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Biomedical subjects

J M Fitzpatrick

Publications and source records attributed to J M Fitzpatrick.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fiducial point placement and the accuracy of point-based, rigid body registration.

OBJECTIVE: To demonstrate that the shape of the configuration of fiducial points is an important factor governing target registration error (TRE) in point-based, rigid registration. METHODS: We consider two clinical situations: cranial neurosurgery and pedicle screw placement. For cranial neurosurgery, we apply theoretical results concerning TRE prediction, which we have previously derived and validated, to three hypothetical fiducial marker configurations. We illustrate the profile of expected TRE for each configuration. For pedicle screw placement, we apply the same theory to a common anatomic landmark configuration (tips of spinous and transverse processes) used for pedicle screw placement, and we estimate the error rate expected in placement of the screw. RESULTS: In the cranial neurosurgery example, we demonstrate that relatively small values of TRE may be achieved by using widely spread fiducial markers and/or placing the centroid of the markers near the target. We also demonstrate that near-collinear marker configurations far from the target may result in large TRE values. In the pedicle screw placement example, we demonstrate that the screw must be approximately 4 mm narrower than the pedicle in which it is implanted to minimize the chance of pedicle violation during placement. CONCLUSION: The placement of fiducial points is an important factor in minimizing the error rate for point-based, rigid registration. By using as many points as possible, avoiding near-collinear configurations, and ensuring that the centroid of the fiducial points is as near as possible to the target, TREs can be minimized.

Brain Diseases↗
PubMed2001

The distribution of target registration error in rigid-body point-based registration.

Guidance systems designed for neurosurgery, hip surgery, spine surgery and for approaches to other anatomy that is relatively rigid can use rigid-body transformations to accomplish image registration. These systems often rely on point-based registration to determine the transformation and many such systems use attached fiducial markers to establish accurate fiducial points for the registration, the points being established by some fiducial localization process. Accuracy is important to these systems, as is knowledge of the level of that accuracy. An advantage of marker-based systems, particularly those in which the markers are bone-implanted, is that registration error depends only on the fiducial localization and is, thus, to a large extent independent of the particular object being registered. Thus, it should be possible to predict the clinical accuracy of marker-based systems on the basis of experimental measurements made with phantoms or previous patients. For most registration tasks, the most important error measure is target registration error (TRE), which is the distance after registration between corresponding points not used in calculating the registration transform. In this paper, we derive an approximation to the distribution of TRE; this is an extension of previous work that gave the expected squared value of TRE. We show the distribution of the squared magnitude of TRE and that of the component of TRE in an arbitrary direction. Using numerical simulations, we show that our theoretical results are a close match to the simulated ones.

Diagnostic Imaging↗
PubMed2000

Heat-shock proteins inhibit induction of prostate cancer cell apoptosis.

BACKGROUND: Resistance to apoptosis remains a significant problem in the treatment of prostate cancer. Heat-shock proteins (HSP) have been correlated with tumor progression. The role of HSP in prostate cancer resistance to apoptosis is unknown. METHODS: PC-3 and LNCaP prostate cancer cells were heat-shocked and then treated with or without diethyl-maleate, etoposide, cycloheximide, or 3 Gray irradiation. Percent apoptosis was assessed by propidium iodide DNA incorporation. Protein was also extracted for analysis by SDS-PAGE Western blotting. RESULTS: Western blotting confirmed an increase in HSP 27 and 72. These cells were resistant to both chemical- and radiation-induced apoptosis. Cycloheximide and specific oligonucleotides to HSP 72 blocked the increased expression of HSP 72 and the resistance to apoptosis. Mcl-1, Bcl-2, Bcl-X(L), and glutathione-S-transferase (GST) expression were increased in a time-dependent manner after heat shock. CONCLUSIONS: This study demonstrates that HSP expression, specifically HSP 72, inhibits apoptosis in prostate tumor cell lines, which may be mediated by the production of survival factors.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study.

BACKGROUND: There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis. We investigated the use of an assay of trypsinogen activation peptide (TAP). METHODS: We undertook a multicentre study in 246 patients (172 with acute pancreatitis [35 with severe disease], 74 controls). We assessed the predictive value of urinary TAP concentrations measured by a validated competitive immunoassay. We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems. TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay. FINDINGS: At 24 h after symptom onset, the median urinary TAP concentration was 37 nmol/L (IQR 17-110) for severe and 15 nmol/L (5-35) for mild disease (p<0.001). The respective values for plasma C-reactive protein were 24 mg/L (3-34) and 25 mg/L (6-75; p=0.208). The sensitivity, specificity, positive predictive, and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were: for TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively, and for C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. 48 h after admission the values for the clinicobiochemical scoring systems were: APACHE II (> or =8), 56%, 64%, 30%, and 85%; Ranson score (> or =3), 89%, 64%, 38%, and 96%; and Glasgow score (> or =3), 77%, 75%, 44%, and 93%. At 48 h, the values for C-reactive protein were 86%, 61%, 37%, and 94% and for TAP were 83%, 72%, 44%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy. INTERPRETATION: Urinary TAP provided accurate severity prediction 24 h after onset of symptoms. This single marker of severity in acute pancreatitis deserves routine clinical application.

Acute Disease↗
PubMed2000

Thiol-mediated apoptosis in prostate carcinoma cells.

BACKGROUND: Glutathione (GSH) maintains an optimum cellular redox potential. Chemical depletion, physical efflux from the cell, or intracellular redistribution of this thiol antioxidant is associated with the onset of apoptosis. The aim of this study was to determine the effects of a thiol-depleting agent, diethylmaleate (DEM), on androgen sensitive and insensitive prostate carcinoma cells. METHODS: LNCaP and PC-3 cell lines were induced to undergo apoptosis by DEM and diamide. Apoptosis was quantified by annexin V binding and propidium iodide incorporation using flow cytometry and was confirmed by DNA gel electrophoresis. Intracellular GSH was quantified using a thiol quantitation kit and the generation of reactive oxygen intermediates was measured using dihydrorhodamine 123. Western blot assessed caspase-3, caspase-8, Bcl-2, and Bcl-XL protein expression. Mitochondrial permeability was measured using DiOC6 and stabilized using bongkrekic acid. RESULTS: DEM and diamide induced apoptosis in both androgen sensitive and insensitive cells. Apoptosis was also induced in an LNCaP transfectant cell line overexpressing Bcl-2. Apoptosis was caspase-3 dependent and caspase-8 independent. Bongkrekic acid partially prevented the effects of DEM on mitochondrial permeability but was unable to prevent the induction of apoptosis. Decreased Bcl-2 and Bci-XL protein expression was observed at the time of initial caspase-3 activation. CONCLUSIONS: This study demonstrates that thiol depletion can be used as an effective means of activating caspase-3 in both androgen sensitive and insensitive prostate carcinoma cells. Direct activation of this effector caspase may serve as a useful strategy for inducing apoptosis in prostate carcinoma cells.

Annexin A5↗
PubMed2000

Stricture formation in Crohn's disease: the role of intestinal fibroblasts.

OBJECTIVE: To determine whether intestinal fibroblasts in patients with Crohn's disease (CD) have an enhanced capacity to reorganize collagen and thus cause stricture formation. SUMMARY BACKGROUND DATA: Stricture formation is a characteristic feature of CD that may distinguish it from other forms of inflammatory bowel disease. Methods Fibroblasts were obtained at surgery from the colon and ileum of patients with CD and ulcerative colitis (UC) and control patients. Primary fibroblast cultures were obtained by explant technique. Fibroblast contractile activity was measured using fibroblast-populated collagen lattices (FPCLs), in which the cultured fibroblasts were seeded in free-floating collagen gel matrices that they reorganize and contract. Fibroblast contractile activity was measured as the reduction of surface area (mm2) of collagen gel matrix at 24-hour intervals for 1 week. RESULTS: Fibroblasts from patients with CD displayed enhanced capacity to contract FPCL when compared to UC and control fibroblasts. This activity was maximal in fibroblasts recovered from strictured regions in CD. Fibroblasts from patients with UC had a contractile capacity similar to that of controls. Hydrocortisone inhibited this in vitro contractile activity in a dose-dependent manner. CONCLUSIONS: Intestinal fibroblasts in CD possess enhanced capacity for collagen reorganization and contractile activity in vitro. This activity may be responsible for stricture formation in CD.

Cell Line↗
PubMed2000

Neutrophil apoptosis is delayed in patients with inflammatory bowel disease.

Delayed neutrophil apoptosis is a feature of persistent acute inflammation. Neutrophil-mediated damage has been shown to be associated with the development of inflammatory bowel disease (IBD). Persistence of these cells both at the colonic site and circulation may further contribute to IBD. The aims of this study were to determine whether neutrophils isolated from IBD patients delay apoptosis and to investigate possible mechanisms involved in this delay. We studied 20 patients with IBD, 13 with Crohn's disease, and 7 with ulcerative colitis, all of whom were undergoing intestinal resection for symptomatic disease. Seventeen patients undergoing elective resection of colon cancer acted as operative controls. Systemic, mesenteric arterial, and mesenteric venous blood was harvested. Neutrophils isolated from patients with IBD showed decreased spontaneous apoptosis compared to cancer patients. Mesenteric venous serum of IBD patients contributed to this delay, which contained higher concentrations of interleukin-8 (IL-8). Pro-caspase 3 expression was also reduced in IBD neutrophils, which may contribute to decreased spontaneous and Fas antibody-induced apoptosis. Neutrophil apoptosis may be altered in Crohn's disease and ulcerative colitis through release of anti-apoptotic cytokines and altered caspase expression. The alterations in cell death mechanisms may lead to persistence of the inflammatory response associated with IBD.

Adolescent↗
PubMed2000

Glutathione depletion-induced neutrophil apoptosis is caspase 3 dependent.

Resolving inflammation is a vital step in preventing the persistence of inflammatory disorders. Neutrophils play a major role in tissue damage associated with an inflammatory response. Their death by apoptosis is central to the final resolution of this response. Thiol depletion with diethylmaleate (DEM) or diamide represent important triggers for neutrophil apoptosis. The mechanism by which this process occurs remains unknown. The apoptotic cascade is associated with a number of cellular changes, including caspase activation and mitochondrial permeability. The aims of this study were to determine the role of mitochondrial permeability and the caspase cascade in thiol depletion-induced neutrophil apoptosis. Total cellular glutathione was reduced by DEM and diamide. This reduction was associated with neutrophil apoptosis and an increase in caspase 3 activity. The effects of DEM were blocked by the caspase 3 inhibitor, Z-DEVD-FMK. Mitochondrial permeability that occurred was also increased during this induction of apoptosis. Bongkrekic acid, a mitochondrial membrane stabilizer, inhibited DEM-induced apoptosis. The inhibitors' effects of LPS or GM-CSF on spontaneous neutrophil apoptosis was reversed by DEM, which was mediated by an increase in caspase 3 activity and independent of mitochondrial disruption. Caspase activation is an important step in glutathione depletion-induced apoptosis in resting and inflammatory neutrophils. Regulation of caspase activity may represent a possible target to trigger apoptosis and resolve inflammatory disorders.

Apoptosis↗
PubMed2000

Registration of physical space to laparoscopic image space for use in minimally invasive hepatic surgery.

While laparoscopes are used for numerous minimally invasive (MI) procedures, MI liver resection and ablative surgery is infrequently performed. The paucity of cases is due to the restriction of the field of view by the laparoscope and the difficulty in determining tumor location and margins under video guidance. By merging MI surgery with interactive, image-guided surgery (IIGS), we hope to overcome localization difficulties present in laparoscopic liver procedures. One key component of any IIGS system is the development of accurate registration techniques to map image space to physical or patient space. This manuscript focuses on the accuracy and analysis of the direct linear transformation (DLT) method to register physical space with laparoscopic image space on both distorted and distortion-corrected video images. Experiments were conducted on a liver-sized plastic phantom affixed with 20 markers at various depths. After localizing the points in both physical and laparoscopic image space, registration accuracy was assessed for different combinations and numbers of control points (n) to determine the quantity necessary to develop a robust registration matrix. For n = 11, average target registration error (TRE) was 0.70 +/- 0.20 mm. We also studied the effects of distortion correction on registration accuracy. For the particular distortion correction method and laparoscope used in our experiments, there was no statistical significance between physical to image registration error for distorted and corrected images. In cases where a minimum number of control points (n = 6) are acquired, the DLT is often not stable and the mathematical process can lead to high TRE values. Mathematical filters developed through the analysis of the DLT were used to prospectively eliminate outlier cases where the TRE was high. For n = 6, prefilter average TRE was 17.4 +/- 153 mm for all trials; when the filters were applied, average TRE decreased to 1.64 +/- 1.10 mm for the remaining trials.

Humans↗
PubMed2000

Spinal dysraphism at MR urography: initial experience.

PURPOSE: To prospectively evaluate the role of magnetic resonance (MR) urography in the radiologic assessment of patients with spinal dysraphism. MATERIALS AND METHODS: Fourteen patients with spinal dysraphism were referred for MR urography with half-Fourier rapid acquisition with relaxation enhancement (RARE) (repetition time msec/echo time msec = 11.9/95) and RARE (2,800/1,100) sequences on a 1.5-T MR machine. Six patients did not tolerate MR urography owing to claustrophobia (n = 4) or flexion deformities (n = 2), giving a final success rate of 57% (eight patients). Two patients had a single kidney (one after nephrectomy, one with a crossed-fused ectopic kidney). Images were jointly assessed by two radiologists and compared with excretory urographic studies. The signal intensity ratio and contrast-to-noise ratio were also calculated. RESULTS: Visualization of the kidneys, pelvicaliceal system, and ureters was better with half-Fourier RARE than with RARE imaging, whereas visualization of the bladder was comparable with both sequences. The mean signal intensity ratios for half-Fourier RARE and RARE sequences, respectively, were 16.2 +/- 3.65 and 19.2 +/- 3.65 (P =. 58, factorial analysis of variance model), whereas the mean contrast-to-noise ratios were 55.4 +/- 5.16 and 47.8 +/- 5.16 (P =. 34). Cortical scarring was depicted more clearly at MR urography than at excretory urography, whereas a renal calculus seen at excretory urography was not detected at MR urography. CONCLUSION: MR urography was feasible in 57% of patients with spinal dysraphism and is a safe, accurate method of evaluating the upper urinary tract.

Adolescent↗
PubMed2000

Altered caspase expression results in delayed neutrophil apoptosis in acute pancreatitis.

Acute pancreatitis (AP) may lead to the development of multiple organ dysfunction syndrome (MODS), especially in severe cases. Resolution of such inflammatory responses is dependent on neutrophil apoptosis. Delays in this apoptotic response are associated with persistent inflammation and subsequent tissue damage. The aim of this study is to determine the effects of AP on neutrophil apoptosis and to investigate the underlying mechanisms involved. Neutrophils and serum were isolated from control (n=10) and from patients with AP (mild, n=35, and severe, n=5). Neutrophil apoptosis was assessed by propidium iodide DNA staining using flow cytometry. Caspase, glutathione-S-transferase (GST), and Mcl-1 protein expression were assessed by SDS-PAGE western blotting. Serum interleukin (IL)-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were measured by ELISA. Neutrophils isolated from patients with AP show a significant delay in spontaneous neutrophil apoptosis. Serum factors contributed to this delay with increases in IL-1beta and GM-CSF. Isolated neutrophils were resistant to Fas antibody-induced apoptosis. Caspases represent a central mechanism for spontaneous and Fas antibody-induced neutrophil apoptosis. Procaspase 3 expression was decreased in mild and severe cases, but this effect was independent of serum factors. Increases in GST expression may also contribute to the antiapoptotic effect. Altered caspase expression may represent an additional factor contributing to delayed neutrophil apoptosis. This may contribute to the development of AP and its related complications.

Acute Disease↗
PubMed1999

Defining an international research agenda for quality of life in men with prostate cancer.

BACKGROUND: While the traditional goal in the management of patients with prostate cancer has been to maximize survival, the recent advent of the medical outcomes movement has underscored the importance of patient-centered issues, such as health-related quality of life (HRQOL). METHODS: In this paper we present a comprehensive approach to the study of HRQOL in men with prostate cancer. We begin by defining HRQOL in general, discussing its measurement, and placing it in the context of prostate cancer. We then describe the primary goals of HRQOL research and present examples of validated instruments. We finish by proposing a quality of life research agenda for the next two decades. RESULTS: Contemporary perspectives on HRQOL are based on the World Health Organization's definition of health as not merely the absence of disease, but as a state of physical, emotional, and social well-being. HRQOL measurement must adhere to the strict methodological principles of survey psychometrics and is best accomplished with any of several validated instruments. Once collected, HRQOL information is useful for prostate cancer patients facing difficult treatment decisions. CONCLUSIONS: A solid foundation for HRQOL research has been built in early- and late-stage prostate cancer. It includes the development of new instruments and the establishment of descriptive data. This groundwork will allow investigators to address more complex research issues, such as interpreting interactions among HRQOL domains, presenting HRQOL data to future patients, optimally timing HRQOL data collection, uncovering innate and alterable factors that influence HRQOL, and exploring the intercultural nuances of HRQOL assessment.

Health↗