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R J Hamilton

Publications and source records attributed to R J Hamilton.

At least 19 recordsLinked to original sources

A model for optimizing normal tissue complication probability in the spinal cord using a generalized incomplete repair scheme.

The purpose of this study was to determine the treatment protocol, in terms of dose fractions and interfraction intervals, which minimizes normal tissue complication probability in the spinal cord for a given total treatment dose and treatment time. We generalize the concept of incomplete repair in the linear-quadratic model, allowing for arbitrary dose fractions and interfraction intervals. This is incorporated into a previously presented model of normal tissue complication probability for the spinal cord. Equations are derived for both mono-exponential and bi-exponential repair schemes, regarding each dose fraction and interfraction interval as an independent parameter, subject to the constraints of fixed total treatment dose and treatment time. When the interfraction intervals are fixed and equal, an exact analytical solution is found. The general problem is nonlinear and is solved numerically using simulated annealing. For constant interfraction intervals and varying dose fractions, we find that optimal normal tissue complication probability is obtained by two large and equal doses at the start and conclusion of the treatment, with the rest of the doses equal to one another and smaller than the two dose spikes. A similar result is obtained for bi-exponential repair. For the general case where the interfraction intervals are discrete and also vary, the pattern of two large dose spikes is maintained, while the interfraction intervals oscillate between the smallest two values. As the minimum interfraction interval is reduced, the normal tissue complication probability decreases, indicating that the global minimum is achieved in the continuum limit, where the dose delivered by the "middle" fractions is given continuously at a low dose rate. Furthermore, for bi-exponential repair, it is seen that as the slow component of repair becomes increasingly dominant as the magnitude of the dose spikes decreases. Continuous low-dose-rate irradiation with dose spikes at the start and end of treatment yields the lowest normal tissue complication probability in the spinal cord, given a fixed total dose and total treatment time, for both mono-exponential and bi-exponential repair. The magnitudes of the dose spikes can be calculated analytically, and are in close agreement with the numerical results.

Algorithms↗

Asymmetric preference of serine proteases toward phosphonate and phosphinate esters.

We have previously reported the asymmetric synthesis of (alpha-aminoalkyl) diphenylphosphonate and phosphinate derivatives designed as inhibitors of chymotrypsin- and elastase-like proteases. This paper reports the first kinetic evaluation of individual epimers of the (alpha-aminoalkyl) diphenylphosphonates as inactivators of chymotrypsin, cathepsin G and neutrophil elastase (HNE). Results show that the (R)-epimers consistently function as more potent irreversible inactivators of their respective target proteases than the corresponding (S)-epimers. Additionally, phosphinate analogues were found to be consistently superior to their diphenylphosphonate counterparts. For example, Cbz. Phe(P)(OPh)-(CH(2))(2)-CO(2)Et inactivates cathepsin G approximately 45-fold more rapidly (k(i)/K(i) = 1.2 x 10(5) M(-1). min(-1)) than the analogous Cbz.Phe(P)(OPh)(2) (2.6 x 10(3) M(-1). min(-1)). Similarly, Cbz.Val(P)(OPh)-(CH(2))(2)-CO(2)Et was found to inactivate HNE some 3-fold more efficiently than Cbz.Val(P)(OPh)(2) (6.5 x 10(3) and 2.0 x 10(3) M(-1). min(-1), respectively).

Cathepsin G↗

A descriptive study of an epidemic of poisoning caused by heroin adulterated with scopolamine.

OBJECTIVE: Adulterants, contaminants, and diluents are all examples of additives to street drugs. Some of these additives may be pharmacologically active; however, it is unusual for them to cause toxic side effects. In the spring of 1995, a new form of heroin appeared in New York City, spreading to other East Coast cities, that was adulterated with scopolamine. It caused severe anticholinergic toxicity in heroin users with patients often presenting to emergency departments in great numbers. This is a report of the demographics and clinical characteristics of the epidemic. METHODS: A combination of prospective and retrospective data collection from the New York City, New Jersey, Delaware Valley, and Maryland Poison Centers. The primary measurements were age, sex, route of drug use, vital signs, signs and symptoms, disposition, and treatment. RESULTS: Of the 370 cases reported to the participating poison centers, 129 were excluded from the final analysis because of insufficient data. Of the patients who used this product, 55% presented with signs and symptoms of heroin toxicity but then became severely agitated with anticholinergic symptoms when naloxone was used to reverse respiratory depression. Nasal insufflation was the route of administration in 34% of the cases. Seizures were rare (3%). Ninety percent required admission, and half were admitted to a critical care unit. CONCLUSIONS: Adulteration of street drugs can lead to toxic epidemics. Poison centers are essential for identification of these trends and are the primary source of information on diagnosis and treatment.

Adolescent↗

Volume rendering quantification algorithm for reconstruction of CT volume-rendered structures: Part I. Cerebral arteriovenous malformations.

Volume rendering is a visualization technique that has important applications in diagnostic radiology and in radiotherapy but has not achieved widespread use due, in part, to the lack of volumetric analysis tools for comparison of volume rendering to conventional visualization techniques. The volume rendering quantification algorithm (VRQA), a technique for three-dimensional (3-D) reconstruction of a structure identified on six principal volume-rendered views, is introduced and described. VRQA involves three major steps: 1) preprocessing of the partial surfaces constructed from each of six volume-rendered images; 2) merging these processed partial surfaces to define the boundaries of a volume; and 3) computation of the volume of the structure from this boundary information. After testing on phantoms, VRQA was applied to CT data of patients with cerebral arteriovenous malformations (AVM's). Because volumetric visualization of the cerebral AVM is relatively insensitive to operator dependencies, such as the choice of opacity transfer function, and because precise volumetric definition of the AVM is necessary for radiosurgical treatment planning, it is representative of a class of structures that is ideal for testing and calibration of VRQA. AVM volumes obtained using VRQA are intermediate to those obtained using axial contouring and those obtained using CT-correlated biplanar angiography (two routinely used visualization techniques for treatment planning for AVM's). Applications and potential expansions of VRQA are discussed.

Algorithms↗

Matching photon and electron fields with dynamic intensity modulation.

A technique was developed to reduce the size and magnitude of the hot and cold spots in the abutting regions of photon and electron fields. The photon and electron fields were set up such that the photon field extended approximately 2 cm into the electron field in the abutting region. The region of the photon beam that overlapped the electron field was modulated using a multileaf collimator, effectively broadening the photon penumbra to make it complimentary to the electron penumbra. The computer calculations were verified using film measurements for abutting a 6 MV photon beam with a 9 MeV electron beam. A uniform dose was achieved at a prespecified depth of 2 cm, and dose uniformity was improved at the specified depth and beyond compared with unmodulated photon beams. A slight increase in dose inhomogeneity was seen at shallower depths. The overall areas of the hot and cold spots were significantly reduced. The technique also reduced the sensitivity of dose homogeneity to setup errors such that the magnitudes of the hot and cold spots were about half of those produced with unmodulated photon beam when an overlap or gap of 4 mm was introduced. The technique was applied to the treatment of a head and neck cancer and a lymphoma involving the right pleura with markedly reduced dose inhomogeneity in the abutting regions.

Computer Simulation↗

Using vascular structure for CT-SPECT registration in the pelvis.

UNLABELLED: The authors outline a method for three-dimensional registration of pelvic CT and 111In-labeled monoclonal antibody capromab pendetide (111In MoAb 7E11.C5) images using 99mTc-labeled red blood cell SPECT data. METHODS: This method of CT-SPECT registration relies on the identification of major blood vessels in the CT and 99mTc SPECT images. The vessels are segmented from the image datasets by outlining them on transverse planar slices using a mouse-based drawing tool. Stacking the transverse outlines provides a three-dimensional representation of the vascular structures. Registration is performed by matching the surfaces of the segmented volumes. Dual isotope acquisition of 111In and 99mTc activities provides precise SPECT-SPECT registration so that registration in three dimensions of the 111In MoAb and CT images is achieved by applying the same transformation obtained from the 99mTc SPECT-CT registration. RESULTS: This method provided accurate registration of pelvic structures and significantly improved interpretation of 111In MoAb 7E11.C5 exams. Furthermore, sites of involvement by prostate cancer suggested by the 111In MoAb examination could be interpreted with the bony and soft tissue (nodal) anatomy seen on CT. CONCLUSION: This method is a general clinical tool for the registration of pelvic CT and SPECT imaging data. There are immediate applications in conformal radiation therapy treatment planning for certain prostate cancer patients.

Angiography↗

An intraoral positioning appliance for stereotactic radiotherapy.

Stereotactic radiotherapy provides the most accurate and effective therapy and protects the adjacent, normal tissues. The head must be positioned the same for all treatments. This article describes the fabrication and application of a noninvasive intraoral appliance that verifies the position of the head to deliver more accurate radiotherapy and protect the adjacent, normal tissues.

Brain Neoplasms↗

Declining rate of cricothyrotomy in trauma patients with an emergency medicine residency: implications for skills training.

OBJECTIVE: To report the change in cricothyrotomy rate with emergency medicine (EM) residency development and to address the implications for training in this skill. METHODS: A retrospective chart review was used to determine the cricothyrotomy rate at a 1,000-bed urban Level-1 trauma center with EM, surgery, and anesthesiology residencies. All adult trauma patient visits to the ED between July 1, 1985, and June 30, 1995, were reviewed. The cricothyrotomy rate was defined as the total number of cricothyrotomies per trauma admissions during a study phase. RESULTS: The study period was divided into 3 phases. Phase 1 (academic years 1985-1989): prior to the inception of the EM residency; phase 2 (academic years 1990-1992): initiation and establishment of the residency; and phase 3 (academic years 1993-1994): full implementation of the EM residency. The cricothyrotoiny rate during phase 1 was 1.8% (95% CI: 1.6 to 2.0), vs 1.1% (95% CI: 0.0 to 2.8) and 0.2% (95% CI: 0.0 to 0.2) during phases 2 and 3, respectively. CONCLUSIONS: The cricothyrotomy rate decreased with the full implementation of the EM residency. Whether this trend was an effect of the presence of an EM faculty and residency training program, a parallel approach to airway management nationwide, or another unidentified factor will require further investigation. Nonetheless, given the increasing rarity of this procedure, it is likely that many EM, surgical, and anesthesiology residents will not acquire clinical experience with this technique during training.

Adult↗

Verification of the omni wedge technique.

The optimal field shape achieved using a multileaf collimator (MLC) often requires collimator rotation to minimize the adverse effects of the scalloped dose distribution the leaf steps produce. However, treatment machines are designed to deliver wedged fields parallel or perpendicular to the direction of the leaves. An analysis of cases from our clinic showed that for 25% of the wedged fields used to treat brain and lung tumors, the wedge direction and optimal MLC orientation differed by 20 degrees or more. The recently published omni wedge technique provides the capability of producing a wedged field with orientation independent of the orientation of the collimator. This paper presents a comparison of the three-dimensional (3D) dose distributions of the omni wedged field with distributions of wedged fields produced using both the universal and dynamic wedge techniques. All measurements were performed using film dosimetry techniques. The omni wedge generated fields closely matched the conventional wedged fields. Throughout 95% of the irradiated volume (excluding the penubra), the dose distribution of the omni wedged field ranged from +5.5 to -3.5 +/- 1.5% of that of the conventionally wedged fields. Calculation of the omni wedged field is as accurate as conventional wedged field calculation when using a 3D treatment planning systems. For two-dimensional treatment planning systems, where one must assume that the omni wedged field is identical to a conventional field, the calculated field and the delivered field differs by a small amount.

Brain Neoplasms↗

Fast iterative algorithms for three-dimensional inverse treatment planning.

Three types of iterative algorithms, algebraic inverse treatment planning (AITP), simultaneous iterative inverse treatment planning (SIITP), and iterative least-square inverse treatment planning (ILSITP), differentiated according to their updating sequences, were generalized to three dimension with true beam geometry and dose model. A rapid ray-tracing approach was developed to optimize the primary beam components. Instead of recalculating the dose matrix at each iteration, the dose distribution was generated by scaling up or down the dose matrix elements of the previous iteration. This significantly increased the calculation speed. The iterative algorithms started with an initial intensity profile for each beam, specified by a two-dimensional pixel beam map of M elements. The calculation volume was divided into N voxels, and the calculation was done by repeatedly comparing the calculated and desired doses and adjusting the values of the beam map elements to minimize an objective function. In AITP, the iteration is performed voxel by voxel. For each voxel, the dose discrepancy was evaluated and the contributing pencil beams were updated. In ILSITP and SIITP, the iteration proceeded pencil beam by pencil beam instead of voxel by voxel. In all cases, the iteration procedure was repeated until the best possible dose distribution was achieved. The algorithms were applied to two examples and the results showed that the iterative techniques were able to produce superior isodose distributions.

Algorithms↗

A three-dimensional algorithm for optimizing beam weights and wedge filters.

An essential step towards optimizing and automating radiation therapy treatment planning is to develop an effective algorithm to find the optimal beam weights and wedge filters for a given set of beam directions and modalities. This problem is solved by introducing a variable transformation based on the universal and omni wedge principles. Instead of directly optimizing an objective function with respect to wedge angles and orientations, each field is first decomposed into a superposition of an open field and two orthogonal wedged fields. This transforms the problem of finding J beam weights, wedge angles, and orientations to that of optimizing a system with 3J beam weights (J open beams and 2J nominal wedged beams), where J is the total number of incident beam directions. An iterative algorithm based on a method originally developed for image reconstruction is used to find the 3J beam weights. The technique is applied to a few clinical cases. Treatment plans are improved compared to those obtained through the conventional manual trial and error planning process. In addition, planning time and effort are greatly reduced.

Algorithms↗

Performance of a video-image-subtraction-based patient positioning system.

PURPOSE: We have developed and tested an interactive video system that utilizes image subtraction techniques to enable high precision patient repositioning using surface features. We report quantitative measurements of system performance characteristics. METHODS AND MATERIALS: Video images can provide a high precision, low cost measure of patient position. Image subtraction techniques enable one to incorporate detailed information contained in the image of a carefully verified reference position into real-time images. We have developed a system using video cameras providing orthogonal images of the treatment setup. The images are acquired, processed and viewed using an inexpensive frame grabber and a PC. The subtraction images provide the interactive guidance needed to quickly and accurately place a patient in the same position for each treatment session. We describe the design and implementation of our system, and its quantitative performance, using images both to measure changes in position, and to achieve accurate setup reproducibility. RESULTS: Under clinical conditions (60 cm field of view, 3.6 m object distance), the position of static, high contrast objects could be measured with a resolution of 0.04 mm (rms) in each of two dimensions. The two-dimensional position could be reproduced using the real-time image display with a resolution of 0.15 mm (rms). Two-dimensional measurement resolution of the head of a patient undergoing treatment for head and neck cancer was 0.1 mm (rms), using a lateral view, measuring the variation in position of the nose and the ear over the course of a single radiation treatment. Three-dimensional repositioning accuracy of the head of a healthy volunteer using orthogonal camera views was less than 0.7 mm (systematic error) with an rms variation of 1.2 mm. Setup adjustments based on the video images were typically performed within a few minutes. The higher precision achieved using the system to measure objects than to reposition them suggests that the variability in repositioning is dominated by the ability of the therapist to make small, controlled changes in the position of the patient. CONCLUSION: Using affordable, off-the-shelf technology, we have developed a patient positioning system that achieves repositioning accuracy normally associated with fractionated stereotactic systems. The technique provides real-time guidance and can be used to easily and quickly correct patient setup before every treatment, thus significantly reducing overall random positioning error. This improved positioning capability provides the precision required to realize the potential gains of conformal radiotherapy.

Computer Terminals↗

Functional imaging in treatment planning of brain lesions.

PURPOSE: Explore the use of functional imaging data in radiation treatment planning of brain lesions. METHODS AND MATERIALS: Compare the treatment-planning process with and without the use of functional brain imaging for clinical cases where functional studies using either single photon emission computed tomography or magnetic resonance imaging are available. RESULTS: A method to register functional image data with planning image studies is needed for functional treatment planning. Functional volumes are not simply connected regions. One activation study may produce many isolated functional areas. After finding the functional volumes and registering the functional information with the planning imaging data, the tools used for conventional three-dimensional treatment planning are sufficient for functional treatment planning. However, the planning system must provide dose-volume histograms for volumes of interest that consist of isolated pieces. Treatment plans that spare functional brain while providing identical target coverage can be constructed for lesions situated near the functional volume. However, the dose to other areas of the brain may be increased. CONCLUSIONS: Functional imaging will make determination of dose response of eloquent areas of the brain possible when combined with volumetric dose information and neuropsychological evaluation prior to and after radiation therapy. Realizing the full potential of functional imaging studies will require improved delineation of activated volumes and determination of the uncertainties in functional volume delineation. Optimization of treatment plans by minimizing dose to volumes activated during functional imaging studies should be used cautiously, because the dose to "silent," but possibly eloquent, brain may be increased.

Brain↗

The case of Baby M: nursing care in an ethical wilderness.

This is a reflective case study of an infant with Down Syndrome and a potentially fatal cardiac defect. It is a story of hope and loss, of silence and learning to speak, and of relinquishing space and standing ground. The purpose of this article is to explore the conflicting claims a neonatal intensive care (NICU) nurse faces in caring for critically ill infants. The questions of "Who speaks?" and "Who listens?" are addressed. The concepts of women's moral development and a nursing definition of voice are included. It is proposed that the conventional feminine voice and the embodied knowledge so integral to expert nursing actually draw strength away from the voice that needs to be permitted into the circle of decision makers when ethical issues are raised in the NICU.

Down Syndrome↗