Biomedical subjects

G A Miller

Publications and source records attributed to G A Miller.

At least 55 records · Page 3Linked to original sources

PubMed1998

Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole.

This magnetoencaphalographic (MEG) study was conducted as part of a multicenter clinical trial to study the efficacy of aripiprazole. Participants included 5 DSM-IV schizophrenia subjects and 10 age-matched normal controls. The schizophrenia subjects underwent a second MEG recording after 8 weeks of open-label treatment with aripiprazole. Overall, control subjects showed no abnormal spontaneous magnetic brain activity. At washout, 3 patients showed increased delta and theta activity along with paraxosymal bitemporal slow waves. In 2 of these patients, the slow waves were generated in the superior temporal plane, as determined by dipole modeling. In the third patient, the slow waves appeared to have been generated at multiple regions throughout the temporal and inferior parietal lobes. As a group, schizophrenia patients, when compared with normal controls, demonstrated significant decreases in alpha peak frequency and power. Following treatment, aripiprazole had a significant normalizing effect on delta and theta activity. Patients on aripiprazole continued to demonstrate significant abnormalities in alpha frequency and power.

Adult↗

PubMed1998

The effect of fixation on the size, shape and summed optical density of endometrial cancer nuclei.

OBJECTIVE: Nuclear morphometric features have been shown to be of prognostic importance in several malignancies including recently, endometrial cancer. The authors attempted to see whether the type of fixation affected nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD). METHODS: Fifty specimens, half air dried and half alcohol fixed, were obtained from 25 consecutive patients with endometrial cancer. Results were compared with the paired samples t-test. Differences among the nuclear morphometric features and histologic grade, stage, and depth of myometrial invasion were studied by one-way analysis of variance. Logistic regression was used to determine if any were independent prognostic features. Image analysis was used to determine NUSZ, NUSH, and NUSD. RESULTS: Mean NUSZ was shown to be significantly larger in air dried specimens (89.13 microm2) as compared to alcohol fixed specimens (80.34 microm2) P=0.047. Mean NUSH was significantly closer to round in air dried specimens (15.21) as compared to alcohol fixed specimens (15.65) P=0.025. There was no significant difference in mean NUSD between air dried (128.61) and alcohol fixed specimens (126.22) P=0.76. Stage, as well as air dried NUSZ, NUSH, and NUSD were all independent predictors of recurrence. In this study none of the nuclear parameters from the alcohol fixed tissues were predictive of recurrence. CONCLUSION: The type of fixation significantly affects the nuclear morphometric parameters of size and shape. While NUSZ, NUSH, and NUSD from air dried specimens were predictive of recurrence, the same parameters from alcohol fixed specimens were not. A larger prospective trial is currently underway to validate these findings.

Analysis of Variance↗

PubMed1997

Selective processing of superimposed objects: an electrophysiological analysis of object-based attentional selection.

We investigated whether object-based attentional selection occurs from grouped-array or spatially-invariant representations. Subjects were presented with colored objects and asked to judge whether a particular color/shape conjunction was present, regardless of whether the color and shape were part of a single object (same-object condition) or occurred on two different objects (different-object condition). RTs and accuracies were recorded for subjects judgments. ERP components, in particular the P1 and N1, were elicited both from the presentation of the target objects and from a post-display probe that was employed as an index of spatial attention. Consistent with predictions of object-based selection models, RTs and accuracies were faster on same than on different object trials. N1s elicited by the target objects and P1s elicited by the post-display probes discriminated between same and different object trials when the two target objects were superimposed. These data are consistent with the proposal that object-based selection is spatially mediated, even in the case of partially overlapping objects. The data are discussed in terms of space- and object-based models of visual selective attention.

Adolescent↗

PubMed1997

Multiple brain atlas database and atlas-based neuroimaging system.

For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.

Anatomy, Artistic↗

PubMed1997

Quantification of p53 in epithelial ovarian cancer.

OBJECTIVE: The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer. METHODS: Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining. RESULTS: The mean follow-up was 37 months (median, 30 months; range 24-55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P < 0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28. 7%) than the tumors of patients with stage I or II disease (mean 8. 36%) (P < 0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P = 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P = 0.006), p53 expression (P = 0.046), and the level of cytoreduction (P < 0.001) were independent prognostic indicators. CONCLUSION: Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas.

Adult↗

PubMed1997

Patterns of regional brain activity differentiate types of anxiety.

Previous studies have reported hemispheric asymmetries in brain activity in anxiety, but the direction of asymmetry has been inconsistent. A distinction between anxious apprehension (e.g., worry) and anxious arousal (e.g., panic), as types of anxiety, may account for some of the discrepancies. To test this proposition, the authors selected participants with self-reported anxious apprehension and experimentally manipulated anxious arousal. Regional brain activity was examined by recording electroencephalograms during rest and during an emotional narrative task designed to elicit anxious arousal. Overall, anxious participants showed a larger asymmetry in favor of the left hemisphere than did controls. In contrast, during the task, anxious participants showed a selective increase in right parietal activity. The results support the hypothesis that anxious apprehension and anxious arousal are associated with different patterns of regional brain activity.

Anxiety↗

PubMed1997

A difference in nuclear morphometry when frozen rather than fresh tissue is studied.

OBJECTIVE: Since the value of nuclear morphometry as a prognostic indicator in gynecologic malignancies is beginning to be explored, the authors attempted to see whether there was a difference in the nuclear morphometric features of size, shape and summed optical density in endometrial cancer when touch preparations were made from fresh versus frozen tissue. METHODS: Fifty specimens were obtained from twenty-five consecutive patients with endometrial cancer. Each patient had an air dried touch preparation made from fresh and frozen tissue. Values were compared using paired samples T-test. Logistic regression was used as a type of multivariate analysis. Nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were calculated by image analysis. RESULTS: Mean NUSZ was shown to be significantly larger in fresh specimens (117.3 microns2) when compared to the frozen specimens (89.3 microns2) p < 0.001. Mean NUSH was significantly closed to round in frozen specimens (15.21) when compared to the fresh specimens (15.55) p = 0.038. Mean NSUD was shown to be significantly larger in frozen specimens (128.6) as compared to fresh specimens (120.2) p = 0.045. Stage, NUSZ was NUSD from fresh tissue were shown to be independent predictors of recurrent disease. CONCLUSION: The type of tissue (fresh versus frozen) from which touch preparations are made is important. Significant differences in NUSZ, NUSH, and NUSD were seen between fresh and frozen specimens. While NUSZ and NUSD from fresh specimens were predictive of recurrence, the same parameters from frozen specimens were not. A larger prospective trial is underway to determine the validity of these preliminary conclusions.

Cell Nucleus↗

PubMed1996

DNA index by image analysis in advanced endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries, affecting an estimated 140,000 women. More than 32,000 women will be diagnosed with endometrial cancer this year in the United States, and approximately 6,000 will die from this disease. METHODS: Twenty consecutive patients, surgically treated, with advanced endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, as well as FIGO stage, grade, and histology. DI was determined using image analysis. RESULTS: Ten of the 20 patients had recurrence of their disease within the 3-year observation period of the study. A DI of > or = 1.2 strongly predicted recurrence of disease (P = 0.002). Increasing histologic grade and an increasing DI were related (P = 0.01). CONCLUSION: Independent of other prognostic indicators, including lymphovascular space invasion, depth of invasion, and histologic type, a tumor with a DI of > or = 1.2, had a significantly increased chance of recurring within the 3-year observation period.

Aged↗

PubMed1996

Germline WT1 mutations in Wilms' tumor patients: preliminary results.

We conducted a comparative study of the prevalence of germline WT1 mutations in patients with Wilms' tumor. Patients in Group 1 have familial Wilms' tumor, bilateral disease, associated urogenital anomalies, and/or second cancers. Those in Group 2 are unilateral, sporadic Wilms' patients without other associated conditions. Patients with aniridia or Denys-Drash syndrome are known to have WT1 alterations, and are excluded from this study. Preliminary results on 96 subjects show that the overall germline WT1 mutation frequency is low (< 5%). The work to date establishes the feasibility of identifying patients with germline WT1 mutations and, in the future, offering genetic predisposition testing to at-risk relatives. However, genetic predisposition testing of children for WT1 mutations raises many ethical, legal, and psychosocial issues; research is needed to evaluate risks and benefits.

Base Sequence↗

PubMed1996

Estrogen and progesterone receptor status as prognostic indicators in patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary.

BACKGROUND: Steroid receptor status as a prognostic indicator in gynecologic malignancies has been a focus of study for almost 20 years. Although shown to be of importance in assessing prognosis in some patients with endometrial cancer, their importance in assessing prognosis in patients with serous cystadenocarcinoma of the ovary is not established. METHODS: All cases of stage IIIc serous cystadenocarcinoma of the ovary operated on by the gynecologic oncology service from January 1, 1981, through December 31, 1989, were evaluated for their estrogen and progesterone receptor status, time to recurrence, length of survival, and level of primary cytoreduction as well as FIGO stage, grade, and histology, Fresh tissue was obtained and frozen at the time of surgery for the steroid assays. RESULTS: Ninety-six patients who had optimal primary cytoreductive surgery for their stage IIIc serous cystadenocarcinomas of the ovary and had their estrogen and progesterone receptor status established were found. Patients with an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein were shown to have a better mean survival (41 months) than patients with estrogen receptor levels greater than 10 fmol/mg cytosol protein (34 months) (P = 0.015). Five-year survival in the former group (38 patients) was 39.5% while 5-year survival in the latter group (58 patients) was 10.3% (P = 0.001). The was no correlation between progesterone status and survival (P > 0.05) in that same cohort of patients. CONCLUSIONS: In patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary, an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein may be indicative of a better prognosis. Progesterone receptor status does not appear to affect survival.

Adult↗

PubMed1996

p53 as a prognostic indicator in endometrial cancer.

BACKGROUND: One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. Although endometrial cancer is the most common gynecologic malignancy in the United States, any connection between it and p53 is just beginning to be explored. METHODS: Forty-six consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. RESULTS: Thirty-five patients had endometrioid adenocarcinomas, 3 had adenosquamous carcinomas, 3 had papillary serous carcinomas, 3 had clear cell carcinomas, and 2 had undifferentiated carcinomas. p53 expression ranged from 0.0 to 55.8% with a mean of 10.7% for the cohort. For the patients with endometrioid carcinomas, the mean p53 expression was 3.9%, while for those with more aggressive histologies it was 32.4% (P < 0.001). Sixteen of the 35 endometrioid tumors (45.7%) stained positive for p53, while 11 of the remaining 12 (91.2%) tumors with more aggressive histologies stained positive (P < 0.01). Increasing histologic grade correlated with an increasing p53 expression (P = 0.006). The percentage of patient tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.01). However, the mean p53 expression was not different between early (stage 1) and advanced (stage 11, III, and IV) cancers (P = 0.55). Utilizing recurrence as the endpoint for multivariate analysis, FIGO stage and p53 expression were the only independent prognostic indicators found. CONCLUSION: p53 expression is more common in more aggressive histologic subtypes than in endometrioid adenocarcinomas. It is an independent prognostic indicator of disease recurrence.

Adult↗

PubMed1996

Proliferation index determined by MIB-1 and recurrence in endometrial cancer.

BACKGROUND: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Stage, grade, DNA index, histologic type, depth of invasion, steroid receptor status, and the presence of positive peritoneal cytology have all been linked to survival. The monoclonal antibody MIB-1 reacts with the same antigen as Ki-67 giving an estimate of proliferation index. The authors investigated whether MIB-1 staining, using image analysis, could be used as a prognostic indicator of recurrence in endometrial carcinoma. METHODS: The tumors from 39 consecutive patients receiving primary surgical therapy for endometrial cancer were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. The patients were followed for a median of 34 months and their charts were reviewed to determine recurrence, histologic type, grade, stage, depth of invasion, and status of peritoneal cytology. RESULTS: Eleven of the 39 patients had recurrence of their disease within the 3-year observation period of this study. Overall, 22 patients had stage I disease, 3 patients had stage II disease, 12 patients had stage III disease, and 2 patients had stage IV disease. MIB-1 staining was not significantly elevated in advanced (stage III and IV) as opposed to early (stage I and II) cancers (P = 0.558). Elevated MIB-1 staining was associated with an increased incidence of recurrence within 24 months of diagnosis (P = 0.002). Patients whose tumors had MIB-1 staining of greater than or equal to 39.0% had an increased chance of recurring over patients whose tumors stained less than 39.0% (P = 0.003). CONCLUSION: In this series of 39 patients with endometrial cancers, MIB-1 monoclonal antibody staining was shown to be a prognostic indicator of recurrence.

Analysis of Variance↗

PubMed1996

Markov texture parameters as prognostic indicators in endometrial cancer.

BACKGROUND: Texture is a descriptive property of a surface distinct from color and shape. Image analysis allows gray-scale images to have their optical texture measured and analyzed. The authors, utilizing image analysis, prospectively studied Markov texture parameters to determine their relevance as prognostic indicators of disease recurrence in endometrial cancer. METHODS: Seventy-four consecutive patients, surgically treated, with endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as 21 Markov parameters. DI and the Markov parameters were quantified using image analysis. RESULTS: Median follow-up for the study population was 31 months with a range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12 patients died from disease during the observation period of the study. Eleven Markov parameters showed significant correlation with increasing FIGO stage (P < 0.05), while 14 Markov parameters showed significant correlation with survival (P < 0.05). Three Markov parameters, difference entropy (P = 0.025), information measure B (P = 0.01), and diagonal moment (P = 0.046), were demonstrated to be independent prognostic indicators along with the more traditional prognostic indicators, stage (P = 0.006), grade (P = 0.029), and depth of myometrial invasion (P = 0.03). CONCLUSION: Image analysis is able to quantify optical texture. Utilizing bivariate correlations and multivariate analysis, three of these parameters were demonstrated to be independent prognostic indicators in endometrial cancer, specifically difference entropy, information measure B, and diagonal moment.

Adult↗

PubMed1996

Tissue factor pathway inhibitor protects the ischemic spinal cord.

Tissue factor pathway inhibitor (TFPI) is a novel agent that binds to tissue factor/VIIa complex and factor-Xa, thereby reducing the effect of tissue factor (TF) on inflammation and the extrinsic pathway of coagulation. We hypothesize that systemic treatment with TFPI may limit ischemia-reperfusion (IR) injury. Our experiment was designed to evaluate the effects of TFPI on IR in the spinal cord. Twenty-three adult New Zealand white rabbits had snare occlusion devices placed circumferentially around the aorta and tunneled to a subcutaneous position. Forty-eight hours later, in the fully awake state, the animals were treated with either TFPI (1 mg/kg bolus followed by a 1-hr infusion of 20 microgram/kg/min), or heparin (100 U/kg bolus) followed by a 1-hr infusion of 10 ml/kg/hr of PBS while controls received phosphate buffered saline (20 ml followed by a 1-hr infusion of 10 ml/kg/hr). The infrarenal aorta was occluded for 21 min in all groups via the snare device. Animals were observed for 3 days and neurologic recovery was graded by the Tarlov criteria. Results were evaluated as percent of animals with hindlimb recovery (Tarlov 3 and 4). At 24 hr postocclusion, 88% of the TFPI-treated animals had recovered neurologic function versus only 20% of heparin-treated animals and 10% of the phosphate buffered saline group (P=0.031 and 0.009, respectively). At 72 hr, 63% of the TFPI animals retained neurologic function versus 20% of heparin-treated animals and 10% of phosphate buffered saline-treated animals (P=0.032, TFPI versus phosphate buffered saline). The mechanism of action of TFPI is not completely understood, yet this drug may hold promise in the prevention of IR injury of the spinal cord.

Animals↗

PubMed1996

Prevention of spinal cord injury after transient aortic clamping with tissue factor pathway inhibitor.

BACKGROUND: Lower limb paralysis that occurs in 11% of patients after treatment of thoracic and thoracoabdominal aortic aneurysms is unpredictable and at present not preventable. The proposed cause for the neurologic changes is believed to be spinal cord ischemia combined with ischemia/reperfusion injury. Recombinant tissue factor pathway inhibitor (rTFPI), a multivalent Kunitz-type inhibitor that binds to tissue factor-VIIa complex, was evaluated. METHODS: The effectiveness of rTFPI as an agent to limit spinal cord ischemia/reperfusion injury was studied in a rabbit spinal cord made ischemic for 20 minutes. rTFPI or phosphate-buffered saline solution (control) was given in randomized blinded fashion at the onset and conclusion of ischemia. Animals underwent neurologic evaluation at 24 hours in a blinded fashion with a modified Tarlov Scale to rate the lower limb paralysis (score of 4 = normal function, score of 0 = complete paralysis). RESULTS: Seventy-five percent of the TFPI-treated animals had Tarlov scores of 3 to 4, whereas only 29% of the animals treated with phosphate-buffered saline solution had such scores (p < 0.0014). Spinal cord histologic findings correlated with the neurologic findings. CONCLUSIONS: We believe that TFPI has unique inhibitory properties that make it an effective agent in limiting postoperative paraplegia associated with spinal ischemia.

Animals↗

PubMed1996

Clinical evaluation of bacterial leakage of endodontic temporary filling materials.

This study was an in vivo comparison of the bacterial leakage associated with three endodontic temporary restorative materials: Cavit, Intermediate Restorative Material (IRM), and TERM. The access openings of 51 endodontically treated teeth were randomly sealed with a 4-mm thickness of one of the three materials. Three wk after placement of each temporary restoration, bacterial leakage was evaluated by sampling from beneath the temporary restoration and then culturing the samples both aerobically and anaerobically. Positive growth occurred in 4 of 14 TERM samples and in 1 of 18 IRM samples. Cavit did not demonstrate leakage in any of the teeth in which it was used. Cavit provided a significantly better seal than TERM over the study period.

Calcium Sulfate↗

PubMed1996

Production of interleukin-1 by polymorphonuclear leukocytes resident in periradicular tissue.

Twenty-one patients undergoing endodontic surgery were identified. Periradicular tissue samples were recovered, and those showing significant numbers of polymorphonuclear leukocyte (PMN) infiltration were prepared for immunoperoxidase identification of interleukin (IL)-1 alpha and IL-1 beta-producing cells using specific polyclonal antibodies. In selected tissue specimens, 90% or more of the PMN's were found to stain positively for IL-1 alpha and IL-1 beta. In addition, significant numbers of plasma cells and tissue histiocytes stained positively for these IL's. Cell suspensions from selected periapical granuloma specimens, as well as from purified peripheral blood PMN's and peripheral blood mononuclear cells, were also subjected to IL-1 quantitation using a commercial ELISA procedure. Such cell suspensions were found to produce significant levels of IL and could be stimulated to produce increased levels after coculture with lipopolysaccharide. These results suggest that PMN's in inflammatory periradicular tissues may be a significant source of IL-1, and their possible roles in the establishment and resolution of periradicular lesions need to be re-evaluated.

Animals↗

PubMed1996

How we think about cognition, emotion, and biology in psychopathology.

The variety of potential relationships assumed between psychological and biological concepts fosters considerable misunderstanding of what our data can tell us. A naively reductionistic view of psychological concepts is prevalent, particularly in the psychopathology literature. A series of examples of the application of psychophysiological methods in studies of cognition, emotion, and psychopathology provides a background for a discussion of these problems. Unwarranted distinctions between cognition and emotion, between classes of measures, and between psychological and biological approaches to understanding normal functioning and psychopathology undermine the ability of cognitive neuroscience to achieve its considerable potential. A nondualistic, nonreductionistic, non-interactive relationship is recommended, with psychological and biological concepts both having central, necessary, and distinct roles.

Cognition↗