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Biomedical subjects

B Williamson

Publications and source records attributed to B Williamson.

At least 37 records · Page 2Linked to original sources

Radiologist-patient interactions: implications for picture archiving and communications systems and teleradiology.

We analyzed radiologist-patient interactions and found that radiologic examinations can be classified into three categories: those involving direct interaction of the radiologist with each patient, those involving interaction of the radiologist with some of the patients, and those that do not involve interaction between the radiologist and the patient. We then analyzed the staff assignments of a large academic radiology practice and a moderate-sized radiology department. Both departments include a full range of inpatient and outpatient procedures. We concluded that about 50% of the radiologists in these practices could interpret examinations at a location independent of the site where the examination was performed. This type of analysis can be helpful in planning for the reengineering of radiology processes following implementation of picture archiving and communications systems (PACS) and teleradiology.

Ambulatory Care↗

Electronic imaging impact on image and report turnaround times.

We prospectively compared image and report delivery times in our Urgent Care Center (UCC) during a film-based practice (1995) and after complete implementation of an electronic imaging practice in 1997. Before switching to a totally electronic and filmless practice, multiple time periods were consistently measured during a 1-week period in May 1995 and then again in a similar week in May 1997 after implementation of electronic imaging. All practice patterns were the same except for a film-based practice in 1995 versus a filmless practice in 1997. The following times were measured: (1) waiting room time, (2) technologist's time of examination, (3) time to quality control, (4) radiology interpretation times, (5) radiology image and report delivery time, (6) total radiology turn-around time, (7) time to room the patient back in the UCC, and (8) time until the ordering physician views the film. Waiting room time was longer in 1997 (average time, 26:47) versus 1995 (average time, 15:54). The technologist's examination completion time was approximately the same (1995 average time, 06:12; 1997 average time, 05:41). There was also a slight increase in the time of the technologist's electronic verification or quality control in 1997 (average time, 7:17) versus the film-based practice in 1995 (average time, 2:35). However, radiology interpretation times dramatically improved (average time, 49:38 in 1995 versus average time 13:50 in 1997). There was also a decrease in image delivery times to the clinicians in 1997 (median, 53 minutes) versus the film based practice of 1995 (1 hour and 40 minutes). Reports were available with the images immediately upon completion by the radiologist in 1997, compared with a median time of 27 minutes in 1995. Importantly, patients were roomed back into the UCC examination rooms faster after the radiologic procedure in 1997 (average time, 13:36) than they were in 1995 (29:38). Finally, the ordering physicians viewed the diagnostic images and reports in dramatically less time in 1997 (median, 26 minutes) versus 1995 (median, 1 hour and 5 minutes). In conclusion, a filmless electronic imaging practice within our UCC greatly improved radiology image and report delivery times, as well as improved clinical efficiency.

Adult↗

Expression of melanocyte-associated markers gp-100 and Melan-A/MART-1 in angiomyolipomas. An immunohistochemical and rt-PCR analysis.

Angiomyolipomas are tumours of uncertain histogenesis, most often occurring in association with the kidney. A characteristic finding is their reactivity with HMB-45, a monoclonal antibody to the melanocyte-associated antigen gp-100. We tested 18 angiomyolipomas for their reactivity with A103, a monoclonal antibody to Melan-A (MART-1), another melanocyte-associated marker, and compared it with HMB-45. All cases were positive with both antibodies, yet most cases showed a more homogeneous staining pattern with A103. Normal kidney was immunohistochemically negative for both antibodies. We also performed RT-PCR assays for gp-100 and Melan-A in 4 of the 18 angiomyolipoma samples and in three normal kidney samples. All 4 angiomyolipoma specimens revealed mRNA for both melanocyte differentiation markers. gp-100 mRNA was found in the samples of normal kidney, but Melan-A mRNA was not. Our study shows that angiomyolipomas express the melanocyte-associated antigens Melan-A and gp-100 at the protein and at the mRNA level, suggesting a true expression of these antigens rather than cross-reacting epitopes. Based on the mRNA expression pattern, immunohistochemical analysis is the preferred method for the detection of gp-100, while Melan-A can be used at the protein and mRNA levels. Our study demonstrates that A103 is a useful marker for the diagnosis of angiomyolipomas.

Angiomyolipoma↗

Computer-integrated revision total hip replacement surgery: concept and preliminary results.

This paper describes an ongoing project to develop a computer-integrated system to assist surgeons in revision total hip replacement (RTHR) surgery. In RTHR surgery, a failing orthopedic hip implant, typically cemented, is replaced with a new one by removing the old implant, removing the cement and fitting a new implant into an enlarged canal broached in the femur. RTHR surgery is a difficult procedure fraught with technical challenges and a high incidence of complications. The goals of the computer-based system are the significant reduction of cement removal labor and time, the elimination of cortical wall penetration and femur fracture, the improved positioning and fit of the new implant resulting from precise, high-quality canal milling and the reduction of bone sacrificed to fit the new implant. Our starting points are the ROBODOC system for primary hip replacement surgery and the manual RTHR surgical protocol. We first discuss the main difficulties of computer-integrated RTHR surgery and identify key issues and possible solutions. We then describe possible system architectures and protocols for preoperative planning and intraoperative execution. We present a summary of methods and preliminary results in CT image metal artifact removal, interactive cement cut-volume definition and cement machining, anatomy-based registration using fluoroscopic X-ray images and clinical trials using an extended RTHR version of ROBODOC. We conclude with a summary of lessons learned and a discussion of current and future work.

Algorithms↗

Lipid peroxidation and the oxidative burst associated with infection of capsicum annuum by botrytis cinerea

A combination of electron paramagnetic resonance (EPR) spectroscopy and analytical chemistry has been used to study the changes in free radical content, transition metal ion status and lipid peroxidation following inoculation of fruits of sweet pepper (Capsicum annuum) with Botrytis cinerea. EPR detected a high concentration of an unidentified free radical associated with the spreading lesion that extends into the surrounding, healthy tissues. In addition, the EPR-detectable iron(III) was highest at the centre of the lesion, again displaying a gradient out into the surrounding tissues. Analyses for aldehydic products of lipid peroxidation were performed to assess the accumulation and potential of these compounds to contribute to the cell death associated with necrotrophic pathogens. In contrast to the spectrum of aldehydes typically observed within peroxidized biological samples, no accumulation of malondialdehyde nor n-hexanal was observed. Instead, high levels of two hydroxyalkenals (4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal) were detected at concentra- tions up to 4000 and 20 000 pmol g- 1, respectively, at the host-pathogen interface. These results are discussed in terms of the likely mechanisms of formation of these aldehydes.

Journal Article↗

Direct coupling of expanded bed adsorption with a downstream purification step.

In the course of developing a cost-effective, scaleable process for the purification of a recombinant protein from Chinese hamster ovary (CHO) suspension cell culture, we investigated direct capture of this molecule using expanded bed adsorption (EBA). EBA combines clarification, purification, and concentration of the product into a single step. The unclarified bioreactor material was directly applied to a STREAMLINE 25 column containing an affinity STREAMLINE adsorbent. This work focused on simplifying the EBA operations and minimizing the overall processing time by running the EBA column unidirectionally, eluting in the expanded bed mode, and coupling the EBA column directly with ion exchange or hydrophobic interaction chromatography. Unidirectional EBA was clearly a simpler unit operation and did not require the use of specialized equipment. The increase in the elution pool volume was insignificant, especially when the EBA column was eluted directly onto the downstream column. Scale-down was simple and could be automated. Coupling of unidirectional EBA with a downstream purification step reduced processing time, equipment requirements and cost.

Adsorption↗

Characterization of human colon cancer antigens recognized by autologous antibodies.

The screening of cDNA expression libraries derived from human tumors with autologous antibody (SEREX) has proven to be a powerful method for defining the structure of tumor antigens recognized by the humoral immune system. In the present study, 48 distinct antigens (NY-CO-1-NY-CO-48) reactive with autologous IgG were identified by SEREX analysis in 4 patients with colon cancer. Sequencing analysis showed that 17 of the cDNA clones were previously uncharacterized molecules and 31 represented known gene products. The individual cDNA clones were analyzed in the following manner: a search for mutations or other structural changes; an analysis of mRNA expression in a panel of normal tissues; and a frequency analysis of the antibody response to the expressed product in the sera of colon cancer patients and normal individuals. The initial analysis showed NY-CO-13 to be a mutated version of the p53 tumor suppressor gene. Three of the 48 antigens showed a differential pattern of mRNA expression, with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and NY-CO-37 and -38 showing a pattern of tissue-specific isoforms. With regard to immunogenicity, 20 of the 48 antigens were detected by allogeneic sera; 14 of these were reactive with sera from both normal donors and cancer patients, and 6 other clones (NY-CO-8, -9, -13, -16, -20 and -38) reacted exclusively with sera from colon cancer patients (ranging from 14% to 27%). Our results on colon cancer illustrate both the complexity and the potential of the SEREX approach for analysis of the humoral immune response against human cancer.

Adult↗

Anatomy-based registration of CT-scan and intraoperative X-ray images for guiding a surgical robot.

We describe new methods for rigid registration of a preoperative computed tomography (CT)-scan image to a set of intraoperative X-ray fluoroscopic images, for guiding a surgical robot to its trajectory planned from CT. Our goal is to perform the registration, i.e., compute a rotation and translation of one data set with respect to the other to within a prescribed accuracy, based upon bony anatomy only, without external fiducial markers. With respect to previous approaches, the following aspects are new: 1) we correct the geometric distortion in fluoroscopic images and calibrate them directly with respect to the robot by affixing to it a new calibration device designed as a radiolucent rod with embedded metallic markers, and by moving the device along two planes, while radiographs are being acquired at regular intervals; 2) the registration uses an algorithm for computing the best transformation between a set of lines in three space, the (intraoperative) X-ray paths, and a set of points on the surface of the bone (imaged preoperatively), in a statistically robust fashion, using the Cayley parameterization of a rotation; and 3) to find corresponding sets of points to the X-ray paths on the surfaces, our new approach consists of extracting the surface apparent contours for a given viewpoint, as a set of closed three-dimensional nonplanar curves, before registering the apparent contours to X-ray paths. Aside from algorithms, there are a number of major technical difficulties associated with engineering a clinically viable system using anatomy and image-based registration. To detect and solve them, we have so far conducted two experiments with the surgical robot in an operating room (OR), using CT and fluoroscopic image data of a cadaver bone, and attempting to faithfully simulate clinical conditions. Such experiments indicate that intraoperative X-ray-based registration is a promising alternative to marker-based registration for clinical use with our proposed method.

Arthroplasty, Replacement, Hip↗

Characterization of tumor necrosis factor-deficient mice.

Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and duration of an inflammatory process-i.e., an anti-inflammatory function. (iii) In contrast to the expectation that TNF+/+ mice and TNF+/- mice would have identical phenotypes, TNF+/- mice showed increased susceptibility to high-dose LPS lethality, increased susceptibility to Candida challenge, and delayed resolution of the C. parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF.

Animals↗

A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.

Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.

Amino Acid Sequence↗

Specificity of volumetric magnetic resonance imaging in detecting hippocampal sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampal formation are useful in detecting unilateral hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. In this pathologic entity, volumetric MRI analysis shows the epileptogenic structure to be atrophic when compared with the normal, nonepileptogenic side. Some authors have suggested that the radiological features of atrophy of medial temporal lobe structures are common in patients with complex partial seizures, but also are seen frequently in other seizure types and can occur even in patients without epilepsy. OBJECTIVE: To determine if seizures originating in extrahippocampal sites cause gliosis, cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We studied 110 patients with chronic epilepsy using volumetric MRI measurements of the hippocampal formation. Seventeen patients had pathologically proven HS, 27 patients had seizures due to extratemporal structural lesions, 15 patients had seizures caused by extrahippocampal temporal lobe lesions, 29 patients had primary generalized epilepsy, and 22 patients had secondary generalized epilepsy. RESULTS: All 17 patients with HS showed significantly reduced absolute hippocampal formation volumes of greater than 2 SDs below the mean of the control groups. The preoperative hippocampal formation volume measurements correlated well with the severity of HS on pathological examination. Hippocampal volumes were within the normal range in all patients with primary generalized epilepsy, secondary generalized epilepsy, extratemporal structural lesions, and extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial temporal structures. Significant reduction in hippocampal volumes is a specific marker for HS.

Adolescent↗

Symptomatic spinal hemangiomas in association with cutaneous hemangiomas. A case report.

STUDY DESIGN: This case report describes a patient with associated vertebral and peripheral vascular malformations presenting with a painful scoliosis. OBJECTIVES: To treat the vertebral osseous lesion successfully with embolization. SUMMARY OF BACKGROUND DATA: Although vertebral vascular malformations are well described, the association with peripheral lesions is uncommon. When associated peripheral vascular malformations occur, they are usually in tissues derived from the same embryonic segment, which was not the case in this instance. METHODS: After investigation with angiography, this patient's vertebral osseous lesion was treated by embolization. RESULTS: This patient's pain has been abolished since embolization. Her scoliosis has not progressed during follow-up. CONCLUSIONS: This case illustrates the association between spinal and peripheral vascular malformations, and that this association is not always metameric. It highlights the fact that invasive procedures other than surgery are a valuable part of the therapeutic armamentarium.

Adolescent↗

High field NMR microscopic imaging of cultivated strawberry fruit.

The experimental conditions required for discrimination of various types of tissue in fruits of cultivated strawberry (Fragaria x Ananassa) at high fields (ca. 7 T) have been investigated. In marked contrast to soft fruits of other species, from which informative images have been derived at high fields using a variety of pulse sequences and acquisition parameters, appreciable image intensities from parenchymal and vascular tissues in healthy strawberry fruits were obtained only with a spin-echo imaging sequence using large sweep widths (ca. 100,000 Hz), and consequently small values for TE ( < 5 ms), indicating predominantly short T2 values for these tissues. Damage caused by infection by the fungal pathogen Botrytis cinerea is readily seen as a result of a large increase in T2 in the infected tissue, whereas ripening processes appear to be characterized primarily by small variations in the T2-weighted contrast and in the relative magnitudes of T1 between vascular and parenchymal tissue. In addition, it was possible selectively to enhance the contributions to images from the achenes ("seeds") by using very short relaxation delays, thereby enhancing T1-dominated contrast mechanisms.

Fruit↗