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Biomedical subjects

W Grant

Publications and source records attributed to W Grant.

At least 19 recordsLinked to original sources
PubMed2001

The F-actin side binding activity of the Arp2/3 complex is essential for actin nucleation and lamellipod extension.

Most eukaryotic cells rely on localized actin polymerization to generate and sustain the protrusion activity necessary for cell movement [1, 2]. Such protrusions are often in the form of a flat lamellipod with a leading edge composed of a dense network of actin filaments [3, 4]. The Arp2/3 complex localizes within that network in vivo [3, 4] and nucleates actin polymerization and generates a branched network of actin filaments in vitro [5-7]. The complex has thus been proposed to generate the actin network at the leading edge of crawling cells in vivo [3, 4, 8]. However, the relative contributions of nucleation and branching to protrusive force are still unknown. We prepared antibodies to the p34 subunit of the Arp2/3 complex that selectively inhibit side binding of the complex to F-actin. We demonstrate that side binding is required for efficient nucleation and branching by the Arp2/3 complex in vitro. However, microinjection of these antibodies into cells specifically inhibits lamellipod extension without affecting the EGF-stimulated appearance of free barbed ends in situ. These results indicate that while the side binding activity of the Arp2/3 complex is required for nucleation in vitro and for protrusive force in vivo, it is not required for EGF-stimulated increases in free barbed ends in vivo. This suggests that the branching activity of the Arp2/3 complex is essential for lamellipod extension, while the generation of nucleation sites for actin polymerization is not sufficient.

Actin-Related Protein 2↗
PubMed2001

Safety and efficacy of repeat transradial access for cardiac catheterization procedures.

To determine the safety and efficacy of repeat transradial cardiac catheterization, 1,362 consecutive transradial procedures were examined. Repeat transradial procedures were identified (group I, n = 73) and compared with index procedures (group II, n = 1,289). Baseline patient characteristics, procedure success rates (100% vs. 97.9%; P = NS), complication rates (0% vs. 0.08%; P = NS), and procedure times (23.9 +/- 27.3 min vs. 18.2 +/- 14.7 min; P = NS) were similar between groups. This study suggests that repeat transradial catheterization procedures can be performed safely and successfully in appropriately selected patients.

Aged↗
PubMed2000

A prospective study of psychological predictors of lumbar surgery outcome.

STUDY DESIGN: Prospective design in which 102 patients were evaluated with a battery of psychological assessment tests 1-2 weeks before surgery, and outcome was assessed 6 months and 1 year after surgery. OBJECTIVES: The study examined whether three aspects of psychological distress (depression, anxiety, and hostility) predict several surgical outcomes (employment status, subjective pain change ratings, and changes in functional abilities). SUMMARY OF BACKGROUND DATA: Surgery for back pain has been shown to yield poor results in 15-45% of patients. Tools are needed to identify those "at risk" for poor outcome. Aspects of emotional distress, including anxiety, depression, and hostility, have been found to be relevant to various illness outcomes (e.g., cancer, heart disease), but their influence has not been prospectively evaluated for back pain surgical outcome. METHODS: Study patients completed measures of distress before surgery, including the Spielberger Trait Anxiety Inventory, Zung Depression Scale, Modified Somatic Perception Questionnaire, and Cook-Medley Hostility Scale. At 1-year follow-up, patients completed pain change ratings, functional abilities measure (Dallas Pain Questionnaire), and questions about employment status. RESULTS: Multivariate regression analyses, controlling for significant demographic variables, found that failure to return to work was predicted by presurgical anxiety (P < 0.001) and depression (P < 0. 01); failure to report improvement in pain was predicted by presurgical somatic anxiety (P < 0.01) and depression (P < 0.058); and failure to report improved functional abilities was predicted by presurgical somatic anxiety (P < 0.01) and depression (P < 0.05). Hostility did not predict any outcome. Regression analyses found a strong predictor to be a combination of the Zung Depression Scale and Modified Somatic Perception Questionnaire, known as the Distress and Risk Assessment Method (DRAM). CONCLUSIONS: These results indicate that screening for presurgical distress is likely to identify those patients at risk for poor outcome. Studies to evaluate whether presurgical psychological treatment improves outcome are warranted.

Adolescent↗
PubMed2000

Transradial cardiac catheterization in elderly patients.

The safety and efficacy of transradial cardiac catheterization in elderly patients is unknown. This study examines procedure success rates for transradial catheterization in appropriately selected patients < 70 (n = 195) and >/= 70 (n = 83) years old. Elderly patients were less likely to be selected for the transradial approach (46% vs. 61%; P = 0.05). Although patients >/= 70 years old were more often female (39.7% vs. 24.1%; P = 0.008) and had a smaller body surface area (1.89 +/- 0.18 vs. 2.01 +/- 0.24 m2; P = 0. 001), procedure success rates did not differ (95.1% vs. 94.8%; P = NS). Procedure-related variables including procedure time (15.4 +/- 12.6 vs. 16.1 +/- 11.6 min; P = NS), amount of radiographic contrast (90.1 +/- 31.9 vs. 86.4 +/- 29.8 cc; P = NS), and number of catheters used (1.5 +/- 0.9 vs. 1.5 +/- 0.7; P = NS) were similar between groups. We conclude that transradial catheterization can be safely and effectively performed in selected elderly patients. Cathet. Cardiovasc. Intervent. 51:287-290, 2000.

Adult↗
PubMed2000

Applying the equivalent uniform dose formulation based on the linear-quadratic model to inhomogeneous tumor dose distributions: Caution for analyzing and reporting.

We apply the concept of equivalent uniform dose (EUD) to our data set of model distributions and intensity modulated radiotherapy (IMRT) treatment plans as a method for analyzing large dose inhomogeneities within the tumor volume. For large dose nonuniformities, we find that the linerar-quadratic based EUD model is sensitive to the linear-quadratic model parameters, alpha and beta, making it necessary to consider EUD as a function of these parameters. This complicates the analysis for inhomogeneous dose distributions. EUD provides a biological estimate that requires interpretation and cannot be used as a single parameter for judging an inhomogeneous plan. We present heuristic examples to demonstrate the dose volume effect associated with EUD and the correlation to statistical parameters used for describing dose distributions. From these examples and patient plans, we discuss the risk of incorrectly applying EUD to IMRT patient plans.

Humans↗
PubMed2000

A clinical evaluation of setup errors for a prostate immobilization system.

A prostate treatment immobilization system was evaluated with respect to setup errors and efficiency for a specific treatment setup. Prostate patients were treated in the prone position with a rectal catheter using the NOMOS intensity modulated radiotherapy system. Immobilization and setup consisted of a Vac-Loktrade mark bag (MED-TEC, Orange City, IO) fitted within a registration carrier box where patients were aligned to the bag using skin marks along the lower leg. Daily setup errors were analyzed using lateral portal films, registration plates mounted to the carrier box, and the pubic symphasis as a bony reference. Two studies were conducted to evaluate setup technique. In the first study, patient setup required 3-5 minutes for patient positioning and the corresponding superior/inferior errors were found to have a standard deviation of 3.5 mm. In the second study, the technique standards were reduced to allow for faster setup times and, consequently, larger errors; setup times were 1-2 minutes and the mean and standard deviation errors were approximately 2 and 5 mm, respectively.

Humans↗
PubMed1999

Transradial cardiac catheterization in patients with prior brachial artery cutdown.

The safety and efficacy of transradial cardiac catheterization in patients with prior ipsilateral brachial cutdown is not known. Using standard techniques we performed transradial catheterization in 278 consecutive patients, of which 63 had prior brachial cutdown. All patients had a strongly palpable radial pulse and a negative Allen's test. Although patients with prior cutdown were older and had a higher incidence of hypertension and prior coronary artery bypass surgery, there was no significant difference in success rates for transradial catheterization (93.6% vs. 95.3%; P = NS). There were no periprocedural complications. Brachial artery occlusion was responsible for only two unsuccessful catheterization attempts. We conclude that, with careful preprocedural screening, ipsilateral transradial cardiac catheterization can be successfully performed in a majority of patients with prior brachial cutdown.

Brachial Artery↗
PubMed1999

Clinical and financial issues for intensity-modulated radiation therapy delivery.

Intensity-modulated radiation therapy (IMRT) is a term applied to a new technology that uses nonuniform radiation beams to achieve conformal dose distributions. This article reviews the use of a commercial system, the Peacock system, which uses a special multileaf collimator (MIMiC) to deliver the dose distribution using arc therapy and segmented fields, similar to a moving strip. Although initially designed for stereotactic radiosurgery, this system has been employed to treat various body sites. More than 300 patients have been treated at our institution in the past 4 years, mainly for cranial, head-and-neck, and prostate tumors. Presently, we treat 40 to 45 patients per day with this technology using two linear accelerators operating with 10 MV and 15 MV x-rays, as Peacock has become a standard therapy procedure. Cases are presented that show the unique ability of IMRT to deliver conformal dose distributions. Why this type of technology can become a standard procedure and why it is cost-effective therapy for both the institution and the patient are discussed.

Brain Neoplasms↗
PubMed1999

Intensity-modulated radiotherapy: first results with this new technology on neoplasms of the head and neck.

Intensity-modulated beam radiotherapy (IMRT) delivers a highly conformal, three-dimensional (3-D) distribution of radiation doses that is not possible with conventional methods. When administered to patients with head and neck tumors, IMRT allows for the treatment of multiple targets with different doses, while simultaneously minimizing radiation to uninvolved critical structures such as the parotid glands, optic chiasm, and mandible. With 3-D computerized dose optimization, IMRT is a vast improvement over the customary trial-and-error method of treatment planning. We retrospectively reviewed the charts of the first 28 head and neck patients at our institution who were treated with IMRT. All had head and neck neoplasms, including squamous cell carcinoma, adenoid cystic carcinoma, paraganglioma, and angiofibroma. Total radiation doses ranged from 1,400 to 7,100 cGy, and daily doses ranged from 150 to 400 cGy/day. A quality assurance system ensured that computer-generated dosimetry matched film dosimetry in all cases. For midline tumors, this system allowed us to decrease the dose to the parotid glands to less than 3,000 cGy. The incidence of acute toxicity was drastically lower than that seen with conventional radiotherapy delivery to similar sites. This is the first report of the application of IMRT strictly to head and neck neoplasms. We discuss the indications, technique, and initial results of this promising new technology. We also introduce the concept of the Simultaneous Modulated Accelerated Radiation Therapy boost technique, which has several advantages over other altered fractionation schemes.

Adolescent↗
PubMed1998

Intensity modulated conformal therapy for intracranial lesions.

The Peacock planning and delivery system was used to create treatment plans and deliver these plans to patients. The system involves an arc therapy delivery of small (2 cm long) slices of radiation combined with indexing of the couch to achieve target coverage. Two clinical examples are shown to demonstrate the system's capability and evaluate the resources required to produce and deliver the plans. One plan is an optic sheath meningioma and the other is a craniopharyngioma that surrounded the optic chiasm. The optic sheath meningioma was treated to 50 Gy in 25 fractions. The treatment involved delivery of two arcs. The total time to set up the patient and deliver the treatment was less than 15 min. Planning and plan validation after computed tomography required approximately 3 days. The patient had 100% restoration of her field of vision and is stable 3 years post therapy. The second patient is a 9-year-old who had a craniopharyngioma which surrounded the optic chiasm. The tumor was treated to 50.4 Gy in 28 fractions and the dose to the optic chiasm was limited to 45 Gy. The treatment required three arcs and total treatment time was less than 20 min. The patient is stable 15 months post therapy. The system is able to create and deliver radiation patterns that are unique. These plans can be created and delivered in times that rival conventional forward planning conformal radiotherapy systems that cannot produce or conveniently deliver such plans.

Child↗
PubMed1998

Family environment, glycemic control, and the psychosocial adaptation of adults with diabetes.

OBJECTIVE: To evaluate whether the family system variables of adults with diabetes relate to the adequacy of metabolic control or the psychosocial adaptation to the illness. RESEARCH DESIGN AND METHODS: A total of 150 insulin-requiring adults were assessed on a single occasion. They completed two family system measures (the Family Environment Scale [FES] and the Diabetes Family Behavior Checklist [DFBC]), two quality-of-life measures (the Diabetes Quality of Life Scale and the Medical Outcomes Study Health Survey-36), and one measure of cognitive appraisal (the Appraisal of Diabetes Scale). Glycemic control was assessed using HbA1c results. Demographic data (age, sex, diabetes type, duration of diabetes, and number of diabetes-related medical complications) were gathered from the patients' charts. RESULTS: Concerning glycemic control, none of the family system measures were significant predictors of HbA1c. Older age and longer duration of diabetes predicted higher HbA1c values. For psychosocial adaptation, when family members behaved in ways that supported the diabetes care regimen (measured by the DFBC), the individual with diabetes was more satisfied with his or her adaptation to the illness and reported less interference in role function due to emotional problems. Family cohesion (measured by the FES) also related to better physical function. Women reported higher levels of diabetes satisfaction. The Appraisal of Diabetes Scale predicted glycemic control and psychosocial adaptation. CONCLUSIONS: For insulin-treated adults with diabetes, family system variables do not relate to glycemic control, but they do relate to psychosocial adaptation. Future work should explore the impact of family-centered interventions on adaptation, sex differences in adaptation, and the use of the Appraisal of Diabetes Scale as a first-line clinical screening tool.

Adaptation, Psychological↗
PubMed1997

Modulated beam conformal therapy for head and neck tumors.

PURPOSE: The goal of modulated-beam conformal therapy is to reduce the dose to healthy tissue and sensitive structures around a uniformly irradiated target volume. Multiple intensity-modulated fields offer improved tissue-sparing dose distributions. New computer-based systems for planning and delivering such treatments may soon be available from different commercial sources that will make the formulation of an intensity-modulated treatment plan and its execution widely available at any treatment facility that has the resources to acquire the necessary equipment. This work reports on a study of the integration of two such systems. METHODS AND MATERIALS: Treatment planning was done using a commercially available inverse planning algorithm based on simulated annealing. The plans arbitrarily assumed nine coplanar x-ray beams at nonopposed gantry angles. Intensity modulation was computed for each beam. The modulated field at each gantry angle was broken down into a series of uniform (nonmodulated) subfields, which could be delivered as a sequence to produce the desired dose distribution. Because a large number of subfields was delivered, a multileaf collimator (MLC) was used for field shaping. This allowed rapid and accurate field shaping for treatments made up of several hundred subfields. Computer control of the MLC and linear accelerator allowed delivery of doses less than .01 Gy per subfield. Treatment was delivered on a prototype, computer-controlled accelerator and MLC system. Resulting dose distributions were analyzed using film and an anatomically specific, homogeneous phantom. RESULTS: The treatment plans were evaluated using dose-volume histogram analysis. The plans provided acceptably uniform irradiation of the target volume without exceeding dose tolerances for nearby critical structures. The plans were successfully delivered by a prototype dynamic MLC. The time needed to deliver a sequence of subfields at one gantry angle ranged from 0.7 to 2.0 min. Isodoses from film agreed reasonably well with planned isodose distributions. CONCLUSIONS: It is feasible to plan and deliver fixed gantry, modulated-beam conformal therapy for head and neck tumors with systems being developed commercially. The planned dose distributions exhibit significant potential for sparing closely spaced normal tissue structures in the head and neck.

Algorithms↗
PubMed1997

A prospective study of centralization of lumbar and referred pain. A predictor of symptomatic discs and anular competence.

STUDY DESIGN: The presence or absence of rapidly centralizing, peripheralizing, or abolishing low back and radiating pain, as identified during a McKenzie mechanical lumbar assessment of patients with chronic lumbar pain, was compared prospectively with discographic pain provocation and anular competency. OBJECTIVES: To evaluate any relation between the responses of centralization and peripheralization with discographic findings. SUMMARY OF BACKGROUND DATA: Centralization of referred pain has been reported as a very common occurrence during McKenzie assessment and treatment. Patients whose pain centralizes have been shown to achieve superior treatment outcomes. A dynamic internal disc model has been hypothesized as an underlying mechanism for centralization that has not been studied previously. METHODS: Patients with chronically disabling low back pain who were referred for discography underwent preliminary blinded McKenzie clinical assessment and were categorized into three groups by their pain response. Patterns, or lack thereof, of pain response were then compared with blinded discographic pain provocation and anular findings. RESULTS: During the McKenzie assessment, the referred pain of 50% centralized with 74% having positive discograms, of which 91% had an intact anulus. The pain of 25% peripheralized only (would not centralize); 69% of these had positive discograms, but only 54% had an intact anulus. The distal pain of 25% did not respond at all, and only 12.5% of these had positive discograms. CONCLUSION: The McKenzie assessment process reliably differentiated discogenic from nondiscogenic pain (P < 0.001) as well as competent from an incompetent anulus (P < 0.042) in symptomatic discs and was superior to magnetic resonance imaging in distinguishing painful from nonpainful discs.

Adult↗
PubMed1997

Gonadotropin-releasing hormone immunoreactivity in the nasal epithelia of adults with Kallmann's syndrome and isolated hypogonadotropic hypogonadism and in the early midtrimester human fetus.

GnRH-secreting neurons are known to originate in the epithelium of the medial olfactory placode, whence they migrate along the axons of the terminal nerve via the forebrain and into the hypothalamus. Synaptic contact between the developing olfactory bulbs and fascicles of the vomeronasal, terminal, and olfactory nerves does not occur in Kallmann's syndrome. Consequently, there is migration arrest of GnRH cells and partial or complete failure of formation of the olfactory bulbs, resulting in severe olfactory deficit and hypogonadotropic hypogonadism. In the present study, using an immunofluorescent, double immunostaining technique and confocal laser scanning microscopy, we observed GnRH-immunoreactive neurons in the hypothalamus of a 14-week-old human fetus. However, migration of GnRH neurons was not complete, and indeed, such cells were seen to be migrating along terminal nerve fascicles beneath the cribriform plate in a 16-week-old fetus. The same immunofluorescent technique demonstrated the presence of GnRH cells in biopsies of nasal mucosa obtained from three adults with Kallmann's syndrome, one normosmic subject with hypogonadotropic hypogonadism, and a eugonadal male cadaver. These findings are consistent with two different interpretations: the nasal GnRH neurons may be vestigial, representing cells that failed to migrate during embryogenesis; alternatively, they may have been generated de novo later in life, a possibility consistent with the recognized plasticity of human postnatal olfactory neuroepithelium. They also reveal that subjects with the normosmic (i.e. non-Kallmann's) form of GnRH deficiency are able to synthesize immunologically recognizable GnRH, implying that failure of GnRH synthesis is not responsible for this type of hypogonadotropic hypogonadism.

Adult↗