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Biomedical subjects

G A Miller

Publications and source records attributed to G A Miller.

At least 19 recordsLinked to original sources

Minimally Invasive Limited Ligation Endoluminal-assisted Revision (MILLER) for treatment of dialysis access-associated steal syndrome.

Dialysis-associated steal syndrome (DASS) is defined as a clinical condition caused by arterial insufficiency distal to the dialysis access owing to diversion of blood into the fistula or graft. The incidence of symptomatic DASS requiring treatment is 1-8%. The etiology is iatrogenic and symptoms are quite debilitating. Banding of the access inflow has largely been abandoned because of the inherent problem with balancing fistula flow with distal flow complicated by a high incidence of subsequent access thrombosis. In this study, we are reporting a modification to the traditional banding procedure, which markedly improves banding outcomes. We are reporting 16 patients who underwent a new standardized minimally invasive banding procedure performed in an outpatient setting with minimal morbidity. This modified banding procedure requires a small (1-2 cm) skin incision for the placement of a ligature and utilizes a 4 or 5 mm diameter endoluminal balloon to achieve and standardize the desired reduction of inflow size. All 16 patients had immediate symptomatic and angiographic improvement after the procedure. Follow-up showed none of the patients had recurrence of symptoms or thrombosis of the access. In our experience, this procedure is an excellent treatment option because of its simplicity and should be considered as a first-line treatment for patients with DASS.

Adult↗

Evaluation of an upper hive entrance for control of Aethina tumida (Coleoptera: Nitidulidae) in colonies of honey bees (Hymenoptera: Apidae).

This investigation was conducted to test whether an upper hive entrance may result in reduced Aethina tumida Murray (Coleoptera: Nitidulidae) population buildup in newly established honey bee, Apis mellifera L., colonies over an 8-mo period. The upper hive entrance consisted of a 3.5-cm-i.d. polyvinyl chloride pipe positioned 20 cm above the hive bottom. Sixteen bee colonies were established using five-frame nucleus hives with a 0.9-kg (2-1b) package of bees with queen. Eight colonies were placed in each apiary, and each colony received one of two treatments: 1) conventional hive lower entrance and 2) modified upper hive entrance. This investigation was conducted in two distant apiaries where A. tumida had been a major problem to local beekeepers for a minimum of 2 yr. Results showed no overall differences between treatment effects on A. tumida counts over the test period, but there was a reduction in bee brood measured in colonies having an upper hive entrance. We conclude that the upper pipe entrance is not recommended in areas where A. tumida are well established and have become problematic. The expected reduction of brood in colonies as a result of using an upper hive entrance will lead to less productive units for honey production and pollination activities. Other control measures will be necessary to maintain tolerable levels of A. tumida in honey bee colonies at high pest densities.

Animals↗

Auditory sensory gating deficit and cortical thickness in schizophrenia.

Both an EEG P50 sensory gating deficit and abnormalities of the temporal lobe structure are considered characteristic of schizophrenia. The standard P50 sensory gating measure does not foster differential assessment of left- and right-hemisphere contributions, but its analogous MEG M50 component may be used to measure gating of distinct auditory source dipoles localizing to left- and right-hemisphere primary auditory cortex. The present study sought to determine how sensory gating ratio may relate to cortical thickness at the site of the auditory dipole localization. A standard auditory paired-click paradigm was used during MEG for patients (n=22) and normal controls (n=11). Sensory gating ratios were determined by measuring the strength of the 50 ms response to the second click divided by that of the first click (S2/S1). Cortical thickness was assessed by two reliable raters using 3D sMRI. Results showed that: (1) patients had a P50 and left M50 sensory gating deficit relative to controls; (2) cortex in both hemispheres was thicker in the control group; (3) in schizophrenia, poorer left-hemisphere M50 sensory gating correlated with thinner left-hemisphere auditory cortical thickness; and (4) poorer right-hemisphere M50 auditory sensory gating ratio correlated with thinner right-hemisphere auditory cortical thickness in patients. The MEG-assessed hemisphere-specific auditory sensory gating ratio may be driven by this structural abnormality in auditory cortex.

Acoustic Stimulation↗

Heat shock protein 27 in the placentas of women with and without severe preeclampsia.

BACKGROUND: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls. METHODS: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27. RESULTS: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046). CONCLUSION: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Adolescent↗

HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up.

OBJECTIVE: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up. METHODS: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients. CONCLUSION: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

Adenocarcinoma, Clear Cell↗

Observation of the charge symmetry breaking d+d-->4He+pi(0) reaction near threshold.

We report the first observation of the charge symmetry breaking d+d-->4He+pi(0) reaction near threshold. Measurements using a magnetic channel (gated by two photons) of the 4He scattering angle and momentum (from time of flight) permitted reconstruction of the pi(0) "missing mass," the quantity used to separate 4He+pi(0) events from the continuum of double radiative capture 4He+gamma+gamma events. We measured total cross sections for neutral pion production of 12.7+/-2.2 pb at 228.5 MeV and 15.1+/-3.1 pb at 231.8 MeV. The uncertainty is dominated by statistical errors. These cross sections arise fundamentally from the down-up quark mass difference and quark electromagnetic effects that contribute in part through meson mixing (e.g., pi(0)-eta) mechanisms.

Journal Article↗

Interpreting abnormality: an EEG and MEG study of P50 and the auditory paired-stimulus paradigm.

Interpretation of neurophysiological differences between control and patient groups on the basis of scalp-recorded event-related brain potentials (ERPs), although common and promising, is often complicated in the absence of information on the distinct neural generators contributing to the ERP, particularly information regarding individual differences in the generators. For example, while sensory gating differences frequently observed in patients with schizophrenia in the P50 paired-click gating paradigm are typically interpreted as reflecting group differences in generator source strength, differences in the latency and/or orientation of P50 generators may also account for observed group differences. The present study examined how variability in source strength, amplitude, or orientation affects the P50 component of the scalp-recorded ERP. In Experiment 1, simulations examined the effect of changes in source strength, orientation, or latency in superior temporal gyrus (STG) dipoles on P50 recorded at Cz. In Experiment 2, within- and between-subject variability in left and right M50 STG dipole source strength, latency, and orientation was examined in 19 subjects. Given the frequently reported differences in left and right STG anatomy and function, substantial inter-subject and inter-hemispheric variability in these parameters were expected, with important consequences for how P50 at Cz reflects brain activity from relevant generators. In Experiment 1, simulated P50 responses were computed from hypothetical left- and right-hemisphere STG generators, with latency, amplitude, and orientation of the generators varied systematically. In Experiment 2, electroencephalographic (EEG) and magnetoencephalographic (MEG) data were collected from 19 subjects. Generators were modeled from the MEG data to assess and illustrate the generator variability evaluated parametrically in Experiment 1. In Experiment 1, realistic amounts of variability in generator latency, amplitude, and orientation produced ERPs in which P50 scoring was compromised and interpretation complicated. In Experiment 2, significant within and between subject variability was observed in the left and right hemisphere STG M50 sources. Given the variability in M50 source strength, orientation, and amplitude observed here in nonpatient subjects, future studies should examine whether group differences in P50 gating ratios typically observed for patient vs. control groups are specific to a particular hemisphere, as well as whether the group differences are due to differences in dipole source strength, latency, orientation, or a combination of these parameters. Present analyses focused on P50/M50 merely as an example of the broader need to evaluate scalp phenomena in light of underlying generators. The development and widespread use of EEG/MEG source localization methods will greatly enhance the interpretation and value of EEG/MEG data.

Adult↗

Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia.

OBJECTIVE: An integrated analysis using Electroencephalography (EEG) and magnetoencephalography (MEG) is introduced to study abnormalities in early cortical responses to auditory stimuli in schizophrenia. METHODS: Auditory responses were recorded simultaneously using EEG and MEG from 20 patients with schizophrenia and 19 control subjects. Bilateral superior temporal gyrus (STG) sources and their time courses were obtained using MEG for the 30-100 ms post-stimulus interval. The MEG STG source time courses were used to predict the EEG signal at electrode Cz. RESULTS: In control subjects, the STG sources predicted the EEG Cz recording very well (97% variance explained). In schizophrenia patients, the STG sources accounted for substantially (86%) and significantly (P<0.0002) less variance. After MEG-derived STG activity was removed from the EEG Cz signal, the residual signal was dominated by 40 Hz activity, an indication that the remaining variance in EEG is probably contributed by other brain generators, rather than by random noise. CONCLUSIONS: Integrated MEG and EEG analysis can differentiate patients and controls, and suggests a basis for a well established abnormality in the cortical auditory response in schizophrenia, implicating a disorder of functional connectivity in the relationship between STG sources and other brain generators.

Acoustic Stimulation↗

p21 and p53 in ovarian carcinoma: their combined staining is more valuable than either alone.

BACKGROUND: Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. Less is known about the importance of p21 expression. The purpose of this study was to determine the value of the combination of p21 and p53 expression in patients with epithelial ovarian malignancies. METHODS: One hundred three consecutive patients with epithelial ovarian carcinoma were studied using snap-frozen tissue specimens. Immunohistochemical staining utilizing the pAb1801 monoclonal antibody to p53 and NCL-WAF-1 monoclonal antibody to p21 was performed. Image analysis was used to determine whether nuclear staining for either antibody was present. In addition to p21 and p53, International Federation of Gynecology and Obstetrics stage, grade, histology, level of cytoreduction, and DNA index were analyzed as prognostic factors. Univariate and multivariate analyses was performed. RESULTS: One hundred three patients were observed for more than 5 years. Immunohistochemical staining for p21 and p53 were significantly inversely related (P = 0.041). Among the patients whose tumors showed p21 staining but no p53 staining, there were no recurrences and all patients were alive at 5-year follow-up. The 5-year survival rate for these patients was significantly better than for the patients with other combinations of p21/p53 staining (P < 0.0001). The DNA index between these 2 groups was not significantly different (P = 0.057). Multivariate analysis shows the combination of p21 and p53 (P = 0.013) staining to be more valuable as a prognostic indicator than either p53 (P = 0.015) or p21 (P = 0.5) alone. CONCLUSIONS: This study confirms the importance of the combination of p21 and p53 nuclear staining in patients with ovarian carcinoma. Cox regression analysis revealed combination of p21 positive and p53 negative to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than either p21 or p53 alone.

Carcinoma↗

Misunderstanding analysis of covariance.

Despite numerous technical treatments in many venues, analysis of covariance (ANCOVA) remains a widely misused approach to dealing with substantive group differences on potential covariates, particularly in psychopathology research. Published articles reach unfounded conclusions, and some statistics texts neglect the issue. The problem with ANCOVA in such cases is reviewed. In many cases, there is no means of achieving the superficially appealing goal of "correcting" or "controlling for" real group differences on a potential covariate. In hopes of curtailing misuse of ANCOVA and promoting appropriate use, a nontechnical discussion is provided, emphasizing a substantive confound rarely articulated in textbooks and other general presentations, to complement the mathematical critiques already available. Some alternatives are discussed for contexts in which ANCOVA is inappropriate or questionable.

Analysis of Variance↗

Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing.

BACKGROUND & AIMS: The optimal strategy for the detection of hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers remains uncertain. We evaluated whether microsatellite instability (MSI) analysis or MSH2 and MLH1 protein immunostaining of tumors will screen individuals efficiently for germline MSH2 and MLH1 testing. METHODS: We performed a case-series study of 114 eligible families enrolled in our high-risk colorectal cancer (CRC) registry. Medical history data were collected on probands and relatives. MSI analysis was performed on proband tumors, and MSH2 and MLH1 protein immunostaining was assessed. Denaturing gradient gel electrophoresis was used to identify germline MSH2 or MLH1 mutations in probands found to have tumors with high-frequency MSI. RESULTS: Tumor tissue and adequate clinical data were available in 109 of the 114 families. Amsterdam criteria and Bethesda guidelines were met by 23% and 70% of the families, respectively. High-frequency MSI was identified in the proband tumors in 47 of the 109 families (43%). Germline MSH2 and MLH1 gene testing was carried out in the probands of 32 of 47 families with MSI-H tumors. Mutations were detected in 16 families (9 in MSH2 and 7 in MLH1) and sequence variants of uncertain significance in 5 families (1 in MSH2 and 4 in MLH1). Germline mutations or sequence variants of uncertain significance were detected in 15 of 19 (79%) of our Amsterdam families and in 6 of 13 (46%) of our non-Amsterdam families with MSI-H tumors. MSH2 and MLH1 protein immunostaining was assessed in 38 of the 47 MSI-H tumors. Unequivocal loss of hMLH1 expression was found in 20 tumors and loss of MSH2 expression in 9 tumors. Corresponding loss of protein expression was seen in 17 of 18 (94%) of tumors from probands with germline mutations or variants. CONCLUSIONS: The detection of high-frequency MSI or the loss of MSH2 or MLH1 immunostaining in CRCs are both useful criteria for selecting high-risk patients who should be tested for germline mutations in MSH2 or MLH1.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

Chiral three-nucleon forces from p-wave pion production.

Production of p-wave pions in nucleon-nucleon collisions is studied according to an improved power counting that embodies the constraints of chiral symmetry. Contributions from the first two nonvanishing orders are calculated. We find reasonable convergence and agreement with data for a spin-triplet cross section in pp-->pppi(0), with no free parameters. Agreement with existing data for a spin-singlet cross section in pp-->pnpi(+) constrains a short-range operator shown recently to contribute significantly to the three-nucleon potential.

Journal Article↗

p53 and bcl-2 in epithelial ovarian carcinoma: their value as prognostic indicators at a median follow-up of 60 months.

OBJECTIVE: p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies. METHODS: One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed. RESULTS: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P < 0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P < 0. 0001) and level of cytoreduction (P < 0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038). CONCLUSION: This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.

Adult↗

Right-posterior face processing anomaly in depression.

Evidence of a right-posterior brain anomaly was found in a study of 19 individuals with major depression and 15 controls. Participants performed a recognition-memory task involving positive, neutral, and negative face and word stimuli. Scalp brain wave topography suggested a region-specific anomaly in the depressed group. Individuals with major depression demonstrated a reduction in the N200 component of the event-related brain potential to faces and not words. Furthermore, results indicate that the regional anomaly is specific to positive facial stimuli. Findings are interpreted in light of a model of regional brain specialization in emotion and psychopathology.

Adult↗

Responding to threat: hemispheric asymmetries and interhemispheric division of input.

This investigation examined how hemispheric asymmetry and interhemispheric processing contribute to attentional biases toward emotional information. Participants (n = 88) named the color of lateralized squares presented concurrently with neutral, positive, or threatening words. A left-hemisphere advantage in color naming was reduced when distractors were emotional, suggesting right-hemisphere priming by emotional stimuli. Furthermore, the advantage of dividing the word and color across visual fields was increased for emotion words when they were frequently presented, indicating a strategic use of interhemispheric division of labor to reduce the distracting effect of emotional words. Finally, participants with high levels of anxious apprehension were most likely to make use of this interhemispheric processing strategy, supporting a processing efficiency theory of cognitive function in anxiety.

Adult↗