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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 109 records · Page 6Linked to original sources

Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients.

We studied the effectiveness of a newly-developed cognitive-behavioral intervention in 15 patients with marked cognitive impairment and behavior disorder. The design was a single-blind test of a neuropsychological intervention, with pre- and post-treatment assessments of personality and social behavior. MS patients underwent neurological examination and neuropsychological testing at baseline. The patients were then randomly assigned to neuropsychological counseling or standard, non-specific supportive psychotherapy. The active 12-week treatment emphasized enhancement of insight through education, social skills training, and behavior modification. All patients were re-examined within 2 weeks of the termination of treatment. Neuropsychological technicians were blind to treatment condition. Both groups showed evidence of cognitive impairment and personality/behavior disorder prior to treatment and were well matched on demographic, disability, and cognitive measures. Patients who underwent neuropsychological counseling showed significant positive response on measures of social behavior (e.g. excessive ego-centric speech) compared to those who underwent standard counseling. We conclude that these data support the use of non-pharmacological, neuropsychological counseling in patients with acquired, MS-associated behavior disorder.

Adult↗

Image restoration with the Viterbi algorithm.

The Viterbi algorithm (VA) is known to given an optimal solution to the problem of estimating one-dimensional sequences of discrete-valued pixels corrupted by finite-support blur and memoryless noise. A row-by-row estimation along with decision feedback and vector quantization is used to reduce the computational complexity of the VA and allow the estimation of two-dimensional images. This reduced-complexity VA (RCVA) is shown to produce near-optimal estimation of random binary images. In addition, simulated restorations of gray-scale images show the RCVA estimates to be an improvement over the estimates obtained by the conventional Wiener filter (WF). Unlike the WF, the RCVA is capable of superresolution and is adaptable for use in restoring data from signal-dependent Poisson noise corruption. Experimental restorations of random binary data gathered from an optical imaging system support the simulations and show that the RCVA estimate has fewer than one third of the errors of the WF estimate.

Algorithms↗

Decreased natural killer cell responses and altered interleukin-6 and interleukin-10 production in alcoholism: an interaction between alcohol dependence and African-American ethnicity.

BACKGROUND: Epidemiological data indicate that among alcoholics African-American men have higher rates of infections compared with white alcoholics. Alcohol is thought to reduce natural killer (NK) cell responses and to alter cellular immunity by changing the relative balance of Th1 versus Th2 cytokine response profiles. However, translation of these basic immunological observations into the clinical setting is limited, and what clinical data are available are contradictory, in part, because of heterogeneity within the alcoholic patient population. Whether ethnic characteristics contribute to variation in the immunological effects of alcohol is not known. METHODS: This study compared NK activity, interleukin (IL)-2-stimulated NK activity, and concanavalin A-stimulated peripheral blood mononuclear cell production of Th1 (IL-12 and IL-2), Th2 (IL-10), and proinflammatory (IL-6) cytokines in 31 hospitalized chronic alcoholic patients and 31 age-matched controls who were stratified on the basis of ethnicity. RESULTS: NK-cell responses were significantly different across the four groups, and African-American alcoholics showed the lowest levels of NK activity (F = 9.5;p < 0.001) and IL-2-stimulated NK activity (F = 2.9; p < 0.05). Compared with the other three groups, African-American alcoholics also showed lower levels of IL-6 (F = 7.2;p < 0.01) and higher levels of IL-10 (F = 4.9;p < 0.05). Stimulated production of IL-2 and IL-12 were similar in the four groups. Regression analyses showed that alcohol dependence and ethnicity predicted NK activity, whereas the interaction between alcohol dependence and ethnicity predicted levels of IL-6 and IL-10. CONCLUSIONS: In summary, the immunological effects of alcohol dependence are modified by ethnicity status, consistent with the increased health risks found in African-American alcoholics.

Adult↗

Sleep and mood during a winter in Antarctica.

Seasonal variations in sleep characteristics and their association with changes in mood were examined in 91 American men and women who spent the 1991 austral winter at three different research stations in Antarctica. Measures of total hours of sleep over a 24-hr period, duration of longest (i.e., "nighttime") sleep event, number of sleep events, time of sleep onset, and quality of sleep remained unchanged over the course of the austral winter (March through October). However, exposure to total darkness based on station latitude was significantly associated with total hours of sleep, duration of longest sleep event, time of sleep onset, and quality of sleep. Reported vigor the previous month was a significant independent predictor of changes in all five sleep measures; previous month's measures of all six POMS subscales were significant independent predictors of sleep quality. Sleep characteristics were significant independent predictors of vigor and confusion the following month; total sleep, longest sleep event, sleep onset and sleep quality were significant independent predictors of tension-anxiety and depression. Changes in mood during the austral winter are preceded by changes in sleep characteristics, but prolonged exposure to the photo-periodicity characteristic of the high latitudes appears to be associated with improved sleep. In turn, mood changes appear to affect certain sleep characteristics, especially sleep quality.

Adult↗

Predictors of behavior and performance in extreme environments: the Antarctic space analogue program.

BACKGROUND: To determine which, if any, characteristics should be incorporated into a select-in approach to screening personnel for long-duration spaceflight, we examined the influence of crewmember social/ demographic characteristics, personality traits, interpersonal needs, and characteristics of station physical environments on performance measures in 657 American men who spent an austral winter in Antarctica between 1963 and 1974. METHODS: During screening, subjects completed a Personal History Questionnaire which obtained information on social and demographic characteristics, the Deep Freeze Opinion Survey which assessed 5 different personality traits, and the Fundamental Interpersonal Relations Orientation-Behavior (FIRO-B) Scale which measured 6 dimensions of interpersonal needs. Station environment included measures of crew size and severity of physical environment. Performance was assessed on the basis of combined peer-supervisor evaluations of overall performance, peer nominations of fellow crew-members who made ideal winter-over candidates, and self-reported depressive symptoms. RESULTS: Social/demographic characteristics, personality traits, interpersonal needs, and characteristics of station environments collectively accounted for 9-17% of the variance in performance measures. The following characteristics were significant independent predictors of more than one performance measure: military service, low levels of neuroticism, extraversion and conscientiousness, and a low desire for affection from others. CONCLUSIONS: These results represent an important first step in the development of select-in criteria for personnel on long-duration missions in space and other extreme environments. These criteria must take into consideration the characteristics of the environment and the limitations they place on meeting needs for interpersonal relations and task performance, as well as the characteristics of the individuals and groups who live and work in these environments.

Adult↗

Detection of cytochrome P450 and other drug-metabolizing enzyme mRNAs in peripheral blood mononuclear cells using DNA arrays.

The purpose of this study was to determine whether the expression of cytochrome P450 (CYP) enzyme mRNAs, other drug-metabolizing enzyme mRNAs, and transporter mRNAs can be detected using DNA arrays. Total RNA was isolated from peripheral blood mononuclear cells of 10 multiple sclerosis patients and 10 age- and sex-matched controls. The mRNA was reverse transcribed to radiolabeled cDNA, and the resultant cDNA was used to probe a DNA array containing several thousand known human genes. The signals corresponding to several CYPs, drug-metabolizing, and transporter mRNAs was substantially above background. The results demonstrate that the DNA array technique has the sensitivity and the selectivity for applications in the pharmaceutical sciences. The mean values for mRNAs of specific CYPs and drug-metabolizing enzymes in peripheral blood cells were compared with reported values for liver. The capabilities of DNA arrays may prove useful for characterizing CYP expression in a variety of clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Total knee arthroplasty ligament balancing and gap kinematics with posterior cruciate ligament retention and sacrifice.

This cadaver study was undertaken to gain insight into the effects that posterior cruciate ligament retention and sacrifice would have on the amount of deformity correction obtained with medial and lateral structure release during total knee arthroplasty. Twenty-seven cadaveric specimens were used to sequentially release medial and lateral structures with and without posterior cruciate support. Each release sequence was tested in full extension and 90 degrees flexion. In full extension, the resulting change into valgus after release of the posterior cruciate ligament, posteromedial capsule/oblique ligament complex, superficial medial collateral ligament, and pes anserinus and semimembranosus tendons was 6.9 degrees, and it increased to 13.4 degrees in 90 degrees flexion. With preservation of the posterior cruciate ligament this decreased to 5.2 degrees in extension and 8.7 degrees in flexion. Changes seen in 90 degrees flexion were significantly greater than those in full extension. For the valgus knee model with release of the posterior cruciate ligament, posterolateral capsule, lateral collateral ligament, iliotibial band, popliteus tendon, and lateral head of the gastrocnemius, 8.9 degrees of change into varus was seen in extension and 18.1 degrees in 90 degrees flexion. With posterior cruciate ligament retention 5.4 degrees and 4.9 degrees of change into varus was seen in extension and flexion, respectively. Significantly less change with retention of the posterior cruciate ligament was seen with both medial and lateral release and more opening of the flexion gap was seen on the release side of the joint for all groups except those with lateral release with sacrifice of the posterior cruciate ligament.

Aged↗

Polysomnographic and spectral sleep EEG in primary alcoholics: an interaction between alcohol dependence and African-American ethnicity.

BACKGROUND: Disturbances of sleep EEG are prominent in alcoholic patients, persist into recovery, and recently have been found to predict those alcoholics who are most likely to relapse. Increasing evidence indicates that there are ethnic differences in sleep EEG and that African-Americans may be at elevated risk for disordered sleep. METHODS: This study compared polysomnographic and spectral sleep EEG measures in male primary alcoholic inpatients (n = 31) and age-matched comparison controls (n = 31) stratified by African-American and Euro-American ethnicity. RESULTS: African-American alcoholic patients showed more severe sleep abnormalities than Euro-American alcoholics, and the interaction between alcohol dependence and ethnicity uniquely contributed to prolonged sleep latency (p < 0.001), loss of delta sleep (p < 0.001), and short rapid eye movement (REM) latency (p < 0.001). Spectral EEG analyses confirmed polysomnographic findings of disordered sleep architecture in alcoholics. Compared with controls, alcoholics had lower delta (0.75-4.5 Hz) activity over the whole night (p < 0.05), reductions in mean spectral power (0.75-40 Hz, p < 0.05), and decreases of delta (p < 0.01) and theta (4.5-7.5 Hz,p = 0.05) activity during the first period of non-REM sleep, with African-American alcoholics having the lowest theta of the four groups. CONCLUSIONS: In view of the possible connection between relapse and poor sleep and the role of sleep in the maintenance of health, these data have implications for treatment and morbidity outcomes in African-American alcoholics.

Adult↗

Injuries and risk factors in an 18-day Marine winter mountain training exercise.

OBJECTIVES: This study determined the incidence of and risk factors for injuries among 356 Marines during a winter mountain training exercise. METHODS: Marines received a podiatry screening and completed a questionnaire on race, education, tobacco use, height, weight, and fitness (4.8-km run, sit-ups, pull-ups). RESULTS: Forty-five Marines (12.6%) reported at least one injury each, 68.9% of which were traumatic injuries. Total injuries resulted in 114 days of limited duty time. A final foot examination (N = 141) revealed 118 injuries (82.2% blisters and abrasions, 11.9% frostnip). White ethnicity was a risk factor for overall injuries, and forefoot varus alignment was a risk factor for traumatic injuries. Lower education and rank and smokeless tobacco use were associated with foot injuries. The Marine ski-march leather boot and smoking were related to foot cold injuries. CONCLUSIONS: Military winter training is associated with injuries and lost training time. Risk factors were identified, suggesting that these injuries may be preventable.

Adult↗

Working in tandem.

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Cooperative Behavior↗

The effect of intraislet somatostatin immunoneutralization on insulin secretion in the isolated perfused rat pancreas.

BACKGROUND: There is evidence of a local inhibitory effect of somatostatin on insulin secretion in the isolated human pancreas, but this has not been shown in a rat model. The possible phasic effect of somatostatin on insulin secretion has not been demonstrated. AIMS: This study was undertaken to determine if somatostatin has a local regulatory effect on phasic insulin secretion within a rat pancreas model. METHODS: The basal and glucose stimulated secretion of insulin was compared with and without immunoneutralization of somatostatin using a somatostatin antibody in an isolated perfused rat pancreas model. High concentration, high affinity monoclonal somatostatin antibody was perfused through isolated rat pancreata. Radioimmunoassay for insulin was performed on the portal effluent. RESULTS: Immunoneutralization of somatostatin during basal insulin secretion produced a rise in insulin secretion of 551 +/- 163% that approached significance. Immunoneutralization during glucose stimulated insulin secretion produced a significant rise in insulin secretion compared to the control group of 2,678 +/- 187% vs. 535 +/- 39% (p < 0.05). The phase I vs. the phase II response in the glucose stimulated pancreas was similar in the presence of control antibody, 867 +/- 351% vs. 900 +/- 398% (p = NS). With somatostatin immunoneutralization, the glucose stimulated pancreas had a significantly higher phase II response than phase I; 3,832 +/- 688% vs. 2,516 +/- 431% (p < 0.05). CONCLUSION: These data indicate that intraislet somatostatin is an inhibitor of insulin secretion in the isolated perfused rat pancreas. This effect occurs primarily in phase II of insulin secretion.

Animals↗

Amitriptyline increases GABA-stimulated 36Cl- influx by recombinant (alpha 1 gamma 2) GABAA receptors.

WSS-1 cells expressing (alpha 1 gamma 2)GABAA receptors show an augmented 36Cl- response to GABA in the presence of amitriptyline that is increased by flumazenil, unlike augmentation by diazepam which is blocked by flumazenil. This amitriptyline effect is opposite to the inhibition of GABA-stimulated 36Cl influx manifested in membrane vesicles prepared from drug-naive rats or submissive rats (a model of depression) but is similar to that seen in tissue from amitriptyline-treated rats or dominant rats. The results suggest a novel mechanism of antidepressant drug action having a delayed onset.

Amitriptyline↗

A comparison of eubacterial and archaeal structure-specific 5'-exonucleases.

The 5'-exonuclease domains of the DNA polymerase I proteins of Eubacteria and the FEN1 proteins of Eukarya and Archaea are members of a family of structure-specific 5'-exonucleases with similar function but limited sequence similarity. Their physiological role is to remove the displaced 5' strands created by DNA polymerase during displacement synthesis, thereby creating a substrate for DNA ligase. In this paper, we define the substrate requirements for the 5'-exonuclease enzymes from Thermus aquaticus, Thermus thermophilus, Archaeoglobus fulgidus, Pyrococcus furiosus, Methanococcus jannaschii, and Methanobacterium thermoautotrophicum. The optimal substrate of these enzymes resembles DNA undergoing strand displacement synthesis and consists of a bifurcated downstream duplex with a directly abutted upstream duplex that overlaps the downstream duplex by one base pair. That single base of overlap causes the enzymes to leave a nick after cleavage and to cleave several orders of magnitude faster than a substrate that lacks overlap. The downstream duplex needs to be 10 base pairs long or greater for most of the enzymes to cut efficiently. The upstream duplex needs to be only 2 or 3 base pairs long for most enzymes, and there appears to be interaction with the last base of the primer strand. Overall, the enzymes display very similar substrate specificities, despite their limited level of sequence similarity.

Archaea↗

Anergy and cytokine-mediated suppression as distinct superantigen-induced tolerance mechanisms in vivo.

Recombinant-activating gene 2 (RAG-2-/-) T cell receptor-transgenic mice repeatedly injected with the superantigen staphylococcal enterotoxin A entered a tolerant state in which splenic CD4+ T cells produced little interleukin (IL)-2, interferon gamma, or IL-4. This state resulted from a combination of both clonal anergy and cytokine-mediated immunosuppression. The anergy persisted for at least 3 wk and could be distinguished from the suppression by a decrease in IL-2 production per cell, a block in the activation of early response kinases, and a failure to be reversed with anti-transforming growth factor (TGF)-beta. Full suppression lasted for only 1 wk and involved both IL-10 and TGF-beta, but required additional unknown molecules for optimal effect. These experiments show that complex in vivo interactions of multiple peripheral tolerance mechanisms can now be dissected at both the cellular and molecular levels.

Animals↗

Meta-analysis of sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive way to diagnose axillary lymph node (ALN) metastases in breast cancer. The most important features are ability to identify the SLN (I.D. rate), how often the SLN and ALN pathology match (concordance), and how often the SLN is negative for cancer when the ALNs are positive (false negative). Technique and patient criteria for SLNB vary among studies. This study performed meta-analysis of published studies to determine the I.D., concordance, and false negative rate (1) overall and for (2) both blue dye and radiocolloid, (3) the injection method, (3) palpable and nonpalpable ALNs, and (4) invasive and in situ disease. METHODS: Inclusion criteria were patients with breast cancer who had SLNB followed by ALN dissection with H&E staining. Meta-analysis was performed using analysis of variance with each observation weighted inversely to its variance. P < 0.05 was considered significant. RESULTS: Eleven studies (n = 912) met the inclusion criteria. Overall, 762 (84%) SLNs were identified, concordance was 747/762 (98%), and 15/296 (5%) were falsely negative. Highest I.D. rates (P < 0.05) were reported with albumin radiocolloid or dye + radiocolloid (97 and 94%, respectively), with injection around an intact tumor (96%), with invasive cancer (95%), and in the clinically negative axilla (96%). Concordance and false negative rates did not vary. CONCLUSIONS: The SLN can be identified in over 97% of patients if certain techniques and inclusion criteria are used. SLNB reflects the status of the axilla in 97% of cases and has a 5% false negative rate.

Adult↗