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Biomedical subjects

L Bauer

Publications and source records attributed to L Bauer.

At least 19 recordsLinked to original sources
PubMed2006

Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes.

OBJECTIVE: To assess efficacy, safety, and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis (MS) (clinically isolated syndrome). METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial. Patients with a first clinical demyelinating event and at least two clinically silent brain MRI lesions were randomized to interferon beta-1b (IFNB-1b) 250 mug subcutaneously (SC) every other day (EOD) (n = 292) or placebo (n = 176), until clinically definite MS (CDMS) was diagnosed or they had been followed for 24 months. RESULTS: After 2 years, 45% of placebo patients had converted to CDMS (Kaplan-Meier estimate; primary outcome measure) and 85% fulfilled the McDonald criteria (co-primary outcome measure). Overall interferon beta-1b delayed the time to diagnosis of CDMS (p < 0.0001) and McDonald MS (p < 0.00001). Hazard ratios (95% CI) were 0.50 (0.36 to 0.70) for CDMS and 0.54 (0.43 to 0.67) for McDonald MS favoring treatment with IFNB-1b. Treatment was well tolerated, as indicated by the low rate of patients dropping out of the study before CDMS was reached (6.6% overall, 7.2% in the IFNB-1b group). CONCLUSIONS: Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinically definite multiple sclerosis, and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis.

Adult↗
PubMed2002

Improvement in activities of daily living in elderly following treatment for post-bereavement depression.

OBJECTIVE: To determine if elderly bereaved depressed subjects display difficulty with activities of daily living (ADL) and if their ADL difficulty improves with psychopharmacologic intervention. METHOD: The Assessment of Motor and Process Skills (AMPS), an ADL assessment measuring ADL motor and ADL process skills, was administered to a pilot sample of elderly persons with post-bereavement depression prior to psychopharmacologic intervention and subsequently during treatment response. RESULTS: In the pretreatment phase, subjects displayed difficulty with ADL motor and ADL process skills that significantly improved during the treatment response phase. CONCLUSION: Results suggest that elderly bereaved depressed individuals demonstrated ADL difficulty that responds positively to psychopharmacologic intervention.

Activities of Daily Living↗
PubMed2001

ras oncogene expression determines sensitivity for intercellular induction of apoptosis.

Fibroblasts carrying an inducible ras oncogene acquire the transformed phenotype after oncogene induction. As a consequence, the transformed cells become sensitive to intercellular induction of apoptosis, a novel regulatory process directed by non-transformed fibroblasts against their transformed descendants. The causal relationship between oncogene expression and sensitivity to intercellular induction of apoptosis is based on extracellular superoxide anion production by oncogene-expressing cells. Superoxide anions (after dismutation to hydrogen peroxide) thereby foster HOCl synthesis and at the same time direct the selectivity of apoptosis induction through hydroxyl generation from HOCl. In parallel, ras expression enhances the sensitivity of fibroblasts for apoptosis-inducing stimuli like cycloheximide, ceramide and mitomycin C. This sensitization seems to be based on a decreased concentration of short lived endogenous apoptosis inhibitors. TGF-beta, like ras induction, decreases the concentration of endogenous apoptosis inhibitors, but does not induce the transformed phenotype. Therefore, TGF-beta treatment alone is not sufficient to render fibroblasts sensitive for intercellular induction of apoptosis, but TGF-beta treatment in parallel with ras activation enhances intercellular induction of apoptosis. Our findings demonstrate that Ras-mediated superoxide anion production determines sensitivity to intercellular induction of apoptosis, whereas the parallel decrease in endogenous apoptosis inhibitors modulates the kinetics of apoptosis induction.

Animals↗
PubMed2001

Analysis of noteworthy indicators on the anesthesia record: a prospective, multiregional study.

A national sample of anesthesia records were studied prospectively for the presence or absence of predetermined, noteworthy record indicators judged important in documenting a basic core of information describing the monitoring and care provided in a generic clinical setting. Only records involving the administration of a volatile anesthetic for the purpose of achieving general anesthesia, prepared by providers with at least 6 months of experience in anesthesia care were examined. No identifying patient, provider, or institutional data were recorded. Indicators were scored in a "present/absent" format. All data were pooled; the goal was to describe the overall phenomena in terms of frequency of compliance. A total of 4,989 anesthesia records were evaluated in terms of 13 record indicators. Those missed ranged from 0.0% (patient identification) to 28.6% (notation regarding emergence). Ten were omitted on less than 6% of the records: 3 (surgery and/or anesthesia start time, notation regarding emergence, surgical positioning noted) were omitted on more han 13.0% of the records. Given he observed inconsistencies, perhaps the anesthesia record needs redesign or the rationale behind documentation requires increased emphasis in educational and equally assurance programs.

Anesthesia↗
PubMed2000

Frontal P300 decrements, alcohol dependence, and antisocial personality disorder.

BACKGROUND: The purpose of this study was to examine the independent and interactive effects of alcohol dependence, antisocial personality disorder (ASPD), and age on brain function. METHODS: P300 event-related potentials (ERPs) were recorded from 393 alcohol-dependent and 170 non-alcohol-dependent adults while they performed a visual oddball task. The two subject groups were further subdivided based upon age and the presence/absence of ASPD. RESULTS: Alcohol dependence was associated with a significant P300 amplitude decrement at anterior electrode sites only. Antisocial personality disorder was also associated with reduced P300 amplitudes at anterior electrode sites; however, the effects were only significant among subjects 30 years of age or younger. To validate this association between ASPD and P300 amplitude a correlational analysis was performed; the correlation between anterior P300 amplitude and the total number of childhood conduct disorder and adult ASPD symptoms was significant. CONCLUSIONS: The P300 amplitude decrement found at anterior electrode sites among subjects with ASPD is consistent with the results of numerous ERP, neuroimaging, or neuropsychologic studies of anterior brain function. Our study is unique in suggesting that the effects of ASPD on anterior brain function are best detected during early adulthood. The study also suggests that the detrimental neurophysiologic effects of alcohol dependence predominantly involve the anterior brain.

Adolescent↗
PubMed2000

Use of complementary medicine by adult patients participating in HIV/AIDS clinical trials.

OBJECTIVE: To identify and characterize patterns of use of complementary and alternative (CAM) therapies by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients participating in clinical trials in a research setting. DESIGN: A descriptive survey using a nonrandom sample of 100 patients was conducted over 17 months, using a 99-item interview schedule adapted from a previous study. SETTING: National Institutes of Health (NIH) Warren G. Magnuson Clinical Center. SUBJECTS: Patients diagnosed with HIV/AIDS, participating in clinical research protocols at the National Institute of Allergy and Infectious Diseases and the National Cancer institute (NCI) at the NIH. RESULTS: Ninety-one percent (91%) had used at least one CAM therapy, as defined by a 1993 study by Eisenberg et al., sometime in their lives. Postdiagnosis, 84% used at least one CAM therapy with an average of just fewer than 5. The increase in frequency of use from 64% prediagnosis was significant (P2 = 0.019). Therapies that became significantly more popular postdiagnosis were, imagery (P2 = 0.00012), high-dose vitamins, (P2 = 0.000019), weight gain (p2 = 0.000244), massage (p2 = 0.00091), relaxation (p2 = 0.0033), herbals (p2 = 0.013), spiritual (p2 = 0.024), and acupuncture (p2 = 0.035). They were primarily used for HIV/AIDS-related problems: dermatological, nausea, depression, insomnia, and weakness. There was a high level of agreement that benefits of CAM use were: feeling better, 51 (98.1%), increased coping, 52 (100%), feeling in control, 44 (88.5%), and enhanced treatment outcome, 49 (94.2%) with 32 (61%) stating CAM was as, or more effective than conventional treatment. Fifty-three percent (53%) were specifically asked by physicians whether they were using adjunct therapies. CONCLUSIONS: Subjects used a variety of CAM therapies to cope with their diseases and rigors of treatment and clinical trials. Further research is needed to identify CAM therapies that may be used as adjunct treatments during clinical trials.

Adult↗
PubMed2000

Responses to rare visual target and distractor stimuli using event-related fMRI.

Previous studies have found that the P300 or P3 event-related potential (ERP) component is useful in the diagnosis and treatment of many disorders that influence CNS function. However, the anatomic locations of brain regions involved in this response are not precisely known. In the present event-related functional magnetic resonance imaging (fMRI) study, methods of stimulus presentation, data acquisition, and data analysis were optimized for the detection of brain activity in response to stimuli presented in the three-stimulus oddball task. This paradigm involves the interleaved, pseudorandom presentation of single block-letter target and distractor stimuli that previously were found to generate the P3b and P3a ERP subcomponents, respectively, and frequent standard stimuli. Target stimuli evoked fMRI signal increases in multiple brain regions including the thalamus, the bilateral cerebellum, and the occipital-temporal cortex as well as bilateral superior, medial, inferior frontal, inferior parietal, superior temporal, precentral, postcentral, cingulate, insular, left middle temporal, and right middle frontal gyri. Distractor stimuli evoked an fMRI signal change bilaterally in inferior anterior cingulate, medial frontal, inferior frontal, and right superior frontal gyri, with additional activity in bilateral inferior parietal lobules, lateral cerebellar hemispheres and vermis, and left fusiform, middle occipital, and superior temporal gyri. Significant variation in the amplitude and polarity of distractor-evoked activity was observed across stimulus repetitions. No overlap was observed between target- and distractor-evoked activity. These event-related fMRI results shed light on the anatomy of responses to target and distractor stimuli that have proven useful in many ERP studies of healthy and clinically impaired populations.

Adult↗
PubMed2000

Use of complementary medicine by adult patients participating in cancer clinical trials.

PURPOSE/OBJECTIVES: To document the prevalence, demographic correlates, patterns of use, and beliefs about complementary and alternative medicine (CAM) therapies of adult patients enrolled in National Cancer Institute (NCI) clinical trials. DESIGN: Prospective, cross-sectional, descriptive survey. SETTING: W.G. Magnuson Clinical Center of the National Institutes of Health in Bethesda, MD. SAMPLE: Convenience sample of 100 English-speaking, adult patients with cancer admitted to intramural clinical trials. METHODS: A standardized, 99-item questionnaire assessing use of CAM therapies pre- and postcancer diagnosis was administered by face-to-face interview. MAIN RESEARCH VARIABLES: Use of CAM therapies, beliefs, communication with physician. FINDINGS: 63% used at least one CAM therapy, with an average use of two therapies per patient. Men were significantly less likely to use a therapy than women; women were more likely to use numerous therapies. Cancer diagnosis seems to have had no influence overall on the frequency of use of CAM therapies. The major reasons stated for CAM use were for treatment-related medical conditions as well as depression, anxiety, and insomnia. The most frequently reported therapies were spiritual, relaxation, imagery, exercise, lifestyle diet (e.g., macrobiotic, vegetarian), and nutritional supplementation. Patients unanimously believed that these complementary therapies helped to improve their quality of life through more effective coping with stress, decreasing the discomforts of treatment and illness, and giving them a sense of control. CONCLUSIONS: Patients with cancer use various complementary therapies to cope with their disease and the rigors of clinical trials. Women and those with higher educational backgrounds were more frequent users. IMPLICATIONS FOR NURSING PRACTICE: Nurses who provide care to subjects of biomedical research have an opportunity and responsibility regarding their patients' use of CAM therapies. Nurses may use in-house resources to help evaluate subjects' use of a CAM modality or to provide quality-of-life therapies such as relaxation, imagery, or healing touch. Discussing these health practices in a nonjudgmental manner adds to the assessment of patients' coping skills and ability to make decisions about their health care.

Adaptation, Psychological↗
PubMed1999

Synthesis and opiate receptor binding properties of 17-methyl-6,7-dehydro-3,14-dihydroxy-4,5alpha-epoxy-6,7:4',5'-pyrimidin omorphinans.

A class of opioid receptor active derivatives of oxymorphone has been synthesized using a common enaminone intermediate. The derivatives have heterocyclic groups fused to the 6,7-positions of the morphinan system and all were synthesized in high yield. A pyrazolo derivative is an agonist for the mu and delta receptors and an antagonist for the kappa receptor.

Morphinans↗
PubMed1999

Respiratory sinus arrhythmia of brainstem lesions.

In this pilot study we investigated the hypothesis that intrinsic and extrinsic brainstem lesions situated within the pontomedullary region would effect the integrity of respiratory sinus arrhythmia. The study sample consisted of three patients with anatomic brainstem abnormalities associated with isolated Chiari I malformation, Chiari II malformation with syringobulbia, and achondroplasia with cervicomedullary compression. They were compared to an age- and sex-matched control group of nine patients. Each subject's electrocardiogram was recorded in a quiet room and digitized by a personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heartrate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. Analysis revealed a significant reduction in respiratory sinus arrhythmia (P < .05), defined as the summated area under the curve, with a mean for controls of 35.42+/-28.13 SD and for subjects of 17.20+/-11.50 SD. There was a gradient of abnormality noted, with the mildest deviation in respiratory sinus arrhythmia for the patient with isolated Chiari I malformation and maximum deviation seen in the patient with extrinsic cervicomedullary compression.

Achondroplasia↗
PubMed1998

Effects of adjuvants on the immune response to allergens in a murine model of allergen inhalation: cholera toxin induces a Th1-like response to Bet v 1, the major birch pollen allergen.

Based on the fact that type I allergies are frequently elicited by inhalant allergens, we have established a model of aerosol inhalation leading to allergic sensitization in BALB/c mice. Using this model we studied the effects of aluminium hydroxide (Al(OH)3), known to enhance IgE antibody responses, compared with cholera toxin (CT), a potent mucosal adjuvant, on the immune response to birch pollen (BP) and its major allergen Bet v 1. Two groups of BALB/c mice were either systemically immunized with recombinant Bet v 1 in Al(OH)3 and subsequently aerosol exposed to BP allergen, or aerosolized with BP and CT. IgE-mediated skin reactions were only elicited in the mice which had received Bet v 1/Al(OH)3. Allergen-specific serum IgE and IgG1 antibodies dominated in the Al(OH)3 group, IgG2a antibody levels to BP and rBet v 1 were markedly higher in the sera of mice exposed to CT with the allergen. IgA antibodies were only detected in the bronchial lavage of the CT-treated group. Moreover, the latter group displayed consistently higher T cell proliferative responses to BP and interferon-gamma production in vitro. Thus, the systemic immunization with rBet v 1 in Al(OH)3 before inhalation of the BP extract promoted a Th2-like immune response, while CT mixed with the aerosolized BP extract rather induced a Th1-like immune response. In an attempt to reverse these ongoing immune responses we could achieve a shift towards a Th0 response. Immunization with BP extract without adjuvant treatment led to undetectable antibody or cellular immune responses. We conclude from the present study that the induction of an immune response to BP allergen after aerosol inhalation can be directed towards a Th1- or a Th2-like response. Once established, the immune response can be modulated.

Adjuvants, Immunologic↗
PubMed1998

Respiratory sinus arrhythmia in children with severe cyanotic and pallid breath-holding spells.

In this study we investigated centrally mediated parasympathetic regulation of modulated cardiac vagal tone among children with severe cyanotic and pallid breath-holding spells by examining respiratory sinus arrhythmia. Respiratory sinus arrhythmia was evaluated in 41 children; 17 subjects with cyanotic breath-holding spells (6 boys, 11 girls; mean age 37.1 months), 7 subjects with pallid breath-holding spells (2 boys, 5 girls; mean age 33.0 months), and 17 controls (8 boys, 9 girls; mean age 41.2 months). Subjects had recurrent (more than 3) severe breath-holding spells. Each subject's electrocardiogram was recorded in a quiet room and digitized by an 80386 personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heart rate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 Hz to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. ANCOVA adjusting for age and sex was conducted with the subject group as the independent measure. There were no significant differences between subjects with cyanotic breath-holding spells and controls. Pallid breath-holding spell subjects had a marked difference in respiratory sinus arrhythmia from either controls or subjects with cyanotic breath-holding spells, demonstrating less variability in respiratory sinus arrhythmia (P < .042) This study supports the hypothesis that there exists autonomic dysregulation in pallid breath-holding spells, caused by a primary central parasympathetic disturbance distinct from the dysregulation found in cyanotic breath-holding spells.

Apnea↗
PubMed1997

Quantitative electroencephalographic differences associated with alcohol, cocaine, heroin and dual-substance dependence.

Resting electroencephalographic (EEG) activity was evaluated in 88 drug-dependent inpatients, abstinent 1-6 months, and 14 non-drug-dependent controls. The patients were assigned to one of four groups using DSM-III-R criteria: alcohol-dependent (n = 12), cocaine-dependent (n = 21), heroin-dependent (n = 19), or dual alcohol- and cocaine-dependent (n = 36). The analysis revealed significant differences between the five subject groups in high- and low-frequency beta power, but not in other frequency bands. Beta power was significantly greater in the alcohol-dependent and cocaine-dependent groups relative to non-drug-dependent controls. These group differences did not correlate with quantity/frequency measures of alcohol or cocaine use, family history, personality, mood, or demographic characteristics. The similar increases in EEG beta found in alcohol- and cocaine-dependent patients do not suggest a direct drug effect. Rather, they suggest the existence of a common premorbid variable or a complex interaction between alcohol/drug use and other variables.

Adult↗
PubMed1997

Effects of some 7-arylidene and 7-heteroarylidene morphinan-6-ones on the antinociceptive activity of [D-Pen2, D-Pen5]enkephalin and [D-Ala2, Glu4]deltorphin II and on multiple opioid receptors.

The in vivo and functional effects of several 7-arylidene and 7-heteroarylidene morphinan-6-ones were determined at the mu-, delta-, and kappa-opioid receptors using the guinea pig brain membranes, guinea pig ileum (GPI), and mouse vas deferens (MVD). In vivo effects included the antagonism by these compounds given subcutaneously on the antinociceptive actions of intracerebroventricularly injected [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Ala2, Glu4]deltorphin II (deltorphin II), the highly selective putative delta 1- and delta 2-opioid receptor agonists. Finally, the partition coefficients of these compounds were estimated (CLOGP) and determined experimentally at pH 7.4 in the 1-octanol/water system. Compared with E-7-benzylidenenaltrexone (BNTX), most compounds except for E-7-(4-chlorobenzylidene)naltrexone, were more potent at delta-opioid receptors than at the mu-opioid receptor, whereas, in comparison to the kappa-opioid receptor, the activities of the E-7-arylidene or E-7-heteroarylidene naltrexone derivatives at the delta-receptor were in the following order, where the 7-substituents were: 4-fluorobenzylidene- > benzylidene > 3-pyridylmethylene- > 4-pyridylmethylene- > 1-methyl-2-imidazolylmethylene > 4-chlorobenzylidene. In the MVD preparation, the potencies at the delta-opioid receptor, in comparison to BNTX, were in the following order, where the 7-substituents were: benzylidene = 1-methyl-2-imidazolylmethylene- > 4-fluorobenzylidene- = 3-pyridylmethylene- = 4-pyridylmethylene-. All compounds antagonized delta 1, and delta 2-opioid receptor agonist-induced analgesia. The antagonist potencies at the delta 1-opioid receptor were in the following order, where the 7-substituents were: benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolymethylene- approximately 4-pyridylmethylene-, whereas at the delta 2-opioid receptor, the order was benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolymethylene- > 4-pyridylmethylene. In general, all compounds exhibited greater potency at the delta 2- than delta 1-opioid receptor. The computed partition coefficients were, as expected, greater than the apparent log P values, which were determined experimentally. Generally, the lipophilicity values in decreasing order were: 4-chlorobenzylidene- > 4-fluorobenzylidene- > benzylidene > 3-pyridylmethylene- = 4-pyridylmethylene- > 1-methyl-2-imidazolylmethylene-. In general, the benzylidene and 4-pyridylmethylene derivatives, which have medium lipophilicities, were equally effective at the delta 1- and delta 2-receptors; the 3-pyridylmethylene and 1-methyl-2-imidazolylmethylene derivatives had lower lipophilicities and were more selective for the delta 2- than delta 1-receptor; the 4-chlorobenzylidene and 4-fluorobenzylidene derivatives were more lipophilic and had intermediate activity. The plot of pED50 values for the in vivo tests for the delta 1- and delta 2-receptors showed that the two receptors are not independent with respect to this series of compounds.

Analgesics↗
PubMed1997

Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1.

Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mice was identified by the use of overlapping peptides. This peptide (BV 139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.

Adjuvants, Immunologic↗