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Biomedical subjects

D Wagner

Publications and source records attributed to D Wagner.

At least 37 records · Page 2Linked to original sources
PubMed2000

The role of tumor necrosis factor in the pathophysiology of heart failure.

Recent studies have focused their attention on the role of the proinflammatory cytokine tumor necrosis factor (TNF) in the development of heart failure. First recognized as an endotoxin-induced serum factor that caused necrosis of tumors and cachexia, it is now recognized that TNF participates in the pathophysiology of a group of inflammatory diseases including rheumatoid arthritis and Crohn's disease. The normal heart does not express TNF; however, the failing heart produces robust quantities. Furthermore, there is a direct relationship between the level of TNF expression and the severity of disease. In addition, both in vivo and in vitro studies demonstrate that TNF effects cellular and biochemical changes that mirror those seen in patients with congestive heart failure. Furthermore, in animal models, the development of the heart failure phenotype can be abrogated at least in part by anticytokine therapy. Based on information from experimental studies, investigators are now evaluating the clinical efficacy of novel anticytokine and anti-TNF strategies in patients with heart failure; one such strategy is the use of a recombinantly produced chimeric TNF alpha soluble receptor. Thus, in view of the emerging importance of proinflammatory cytokines in the pathogenesis of heart disease, we review the biology of TNF, its role in inflammatory diseases, the effects of TNF on the physiology of the heart and the development of clinical strategies that target the cytokine pathways.

Animals↗
PubMed2000

c-Fos expression in the cholinergic basal forebrain after enforced wakefulness and recovery sleep.

The present study used c-Fos expression to examine cellular activity in cholinergic regions in the basal forebrain (BF) following enforced waking and recovery sleep. Cholinergic cells within the vertical and horizontal limbs of the diagonal band of Broca (VDB and HDB, respectively) showed significantly higher c-Fos immunoreactivity after prolonged waking than after recovery sleep. Cholinergic cells within the medial septal nucleus (MS), however, showed no change in c-Fos expression under these conditions. Consistent with our previous findings, c-Fos immunoreactivity in the ventral lateral preoptic area (VLPO) was increased after 1-2h of recovery sleep compared with enforced waking. These results indicate state-specific effects on transcription and subsequent protein expression in cell populations associated with behavioral state and further show that the HDB, VDB and VLPO are good candidates for the further study of intracellular events associated with sleep and wakefulness.

Animals↗
PubMed2000

[A new technique for laparoscopic placement of the adjustable gastric band (LAP-band) for preventing slippage].

BACKGROUND: Slippage (SP) of the stomach is the most common postoperative complication after laparoscopic adjustable silicone gastric banding (LAS-GB) for morbid obesity. METHODS AND PATIENTS: A randomized prospective study was constructed in order to determine whether laparoscopic placement behind the cardia (RKP) is associated with a lower incidence of postoperative SP and pouch dilation than after a retrogastric placement (RGP) of the LAP band using a common technique. Morbidly obese patients presenting for LASGB were randomized to undergo either an RKP (n = 50) or an RGP (n = 51). RESULTS: There were three postoperative SP and three pouch dilations in the RGP group versus no postoperative complication in the RKP group. CONCLUSIONS: The placement of LAP band by the RKP technique is safe and followed by a lower frequency of postoperative complications than with the RGP technique. Clear anatomical landmarks are a benefit to the education and learning curve of LASGB.

Adolescent↗
PubMed2000

[Family study of patients with aspirin intolerance and rhinosinusitis].

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Adolescent↗
PubMed2000

Social desirability scores are associated with higher morning cortisol levels in firefighters.

OBJECTIVE: To examine the association of social desirability (SD) responding ("defensiveness") and cortisol levels. METHODS: Marlowe-Crowne SD scores and morning salivary cortisol were measured in firefighters. RESULTS: SD scores were associated with higher cortisol levels (r=.28) in 60 firefighters under age 45, but not in 25 older firefighters (or the combined sample). CONCLUSION: The results are consistent not only with SD scores being an indicator of coarctation of experience as a coping mechanism, but also (at least for younger persons) perhaps a risk factor for the psychobiological dysfunctions associated with chronic elevations of cortisol.

Adaptation, Psychological↗
PubMed2000

Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used antipyretic agents that most probably exert their antifever effect by inhibiting cyclooxygenase (COX)-2. Thus, COX-2-selective drugs or null mutation of the COX-2 gene reduce or prevent fever. Acetaminophen is antipyretic and analgesic, as are NSAIDs, but it lacks the anti-inflammatory and anticoagulatory properties of these drugs. This has led to the speculation that a COX variant exists that is inhibitable by acetaminophen. An acetaminophen-inhibitable enzyme is inducible in the mouse J774.2 monocyte cell line. Induction of acetaminophen-inhibitable prostaglandin E(2) synthesis parallels induction of COX-2. Thus, inhibition of pharmacologically distinct COX-2 enzyme activity by acetaminophen may be the mechanism of action of this important antipyretic drug.

Acetaminophen↗
PubMed2000

The impact of long-term acute-care facilities on the outcome and cost of care for patients undergoing prolonged mechanical ventilation.

OBJECTIVES: To compare the 6-month mortality rate of chronically ventilated patients treated either exclusively in a traditional acute-care hospital or transferred during hospitalization to a long-term acute-care facility. To analyze the hospital cost of care and estimate the amount of uncompensated care incurred by acute-care hospitals under the Medicare prospective payment diagnostic related groups system. DESIGN: Retrospective chart review and questionnaire. SETTING: Fifty-four acute-care referral hospitals and 26 longterm acute-care institutions. PATIENTS: A total of 432 ventilated patients selected from 3,266 patients referred but not transferred to a study long-term acute-care facility and 1,702 ventilated patients from 4,174 patients referred and then subsequently transferred to the long-term acute-care facility. Six-month outcomes were determined for the subgroup of patients > or =65 yrs old (279 and 1,340 patients, respectively). Hospital charges were available for 192 of the 279 nontransferred patients who were > or =65 yrs old and 1,332 of the 1,340 transferred patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 6-month mortality rate was 67.4% for the 279 nontransferred patients and 67.2% for the 1,340 transferred patients. On multiple regression analysis, variables associated with the 6-month mortality rate included initial admitting diagnosis, age, the acute physiology score, and presence of decubitus ulcer. After controlling for these variables, there was no significant difference in 6-month mortality rate, but admission to the long-term acute-care facility was associated with a longer mean survival time. Average total hospital costs for the 192 nontransferred patients was $78,474, and estimated Medicare reimbursement was $62,472, resulting in an average of $16,002 of uncompensated care per patient. Estimated costs for the long-term acute-care facility admissions were $56,825. CONCLUSIONS: Patients undergoing prolonged ventilation have high hospital and 6-month mortality rates, and 6-month outcomes are not significantly different for those transferred to long-term acute-care facilities. These patients generate high costs, and acute-care hospitals are significantly underreimbursed by Medicare for these costs. Acute-care hospitals can reduce the amount of uncompensated care by earlier transfer of appropriate patients to a long-term acute-care facility.

Aged↗
PubMed2000

In vivo microscopic evaluation of the microvascular behavior of FITC-labeled macromolecular MR contrast agents in the hamster skinfold chamber.

RATIONALE AND OBJECTIVES: The extravasation properties of two macromolecular MR imaging contrast media (CM) in relation to structural differences of the terminal vascular bed were investigated to determine whether differentiation between normal (physiological) and tumor (pathological) tissue can be achieved by means of extravasation characteristics. METHODS: Gd-DTPA-polylysine (50 kD, CM1) and Gd-DOTA cascade polymer (Gadomer 17; 20 kD, CM2) were labeled with fluorescein isothiocyanate (FITC) to enable in vivo fluorescence microscopy of the microcirculation. After implantation of a dorsal skinfold chamber and 7 days (range, 6-8) after induction of an amelanotic melanoma (A-Mel-3), 14 male hamsters weighing 85 g (range, 70-95 g) received 200 micromol/kg of CM1 by intravenous injection into the jugular vein. CM2 was similarly investigated after an interval of 24 hours. Fluorescence microscopy was performed in areas of subcutaneous tissue, striated muscle, and tumor tissue. Microscopic images were registered by a charge-coupled-device video camera and transferred to a video system. Distribution intensities of CM were evaluated on a digitally based measurement system. A control investigation was performed with FITC-dextran (150 kD). RESULTS: Gd-DTPA-polylysine showed no extravasation into physiological tissue for the first 10 minutes after injection. After this period, however, the first signs of leakage became apparent. Gd-DOTA cascade polymer was extravasated after 5 minutes into the tumor-free tissue. In tumor capillaries, Gd-DTPA-polylysine could be detected in the extravasal space as well as in physiological tissue after 15 minutes. After injection of Gd-DOTA cascade polymer, direct leakage from tumor capillaries was observed, with a contrast maximum between tumor and surrounding tissue occurring 3 to 5 minutes after CM injection. Good delineation of tumor vascularization from striated muscle and subcutaneous tissue was achieved. CONCLUSIONS: The CM studied showed different microvascular permeation properties. Faster leakage of Gd-DOTA cascade polymer was observed in areas with neoplastic tumor vessels, whereas extravasation in physiological tissue was detected after a period of 5 minutes. Gd-DTPA-polylysine demonstrated nonspecific leakage at later time points.

Animals↗
PubMed2000

Prediction of survival for older hospitalized patients: the HELP survival model. Hospitalized Elderly Longitudinal Project.

OBJECTIVE: To develop and validate a model estimating the survival time of hospitalized persons aged 80 years and older. DESIGN: A prospective cohort study with mortality follow-up using the National Death Index. SETTING: Four teaching hospitals in the US. PARTICIPANTS: Hospitalized patients enrolled between January 1993 and November 1994 in the Hospitalized Elderly Longitudinal Project (HELP). Patients were excluded if their length of hospital stay was 48 hours or less or if admitted electively for planned surgery. MEASUREMENTS: A log-normal model of survival time up to 711 days was developed with the following variables: patient demographics, disease category, nursing home residence, severity of physiologic imbalance, chart documentation of weight loss, current quality of life, exercise capacity, and functional status. We assessed whether model accuracy could be improved by including symptoms of depression or history of recent fall, serum albumin, physician's subjective estimate of prognosis, and physician and patient preferences for general approach to care. RESULTS: A total of 1266 patients were enrolled over a 10-month period, (median age 84.9, 61% female, 68% with one or more dependency), and 505 (40%) died during an average follow-up of more than 2 years. Important prognostic factors included the Acute Physiology Score of APACHE III collected on the third hospital day, modified Glasgow coma score, major diagnosis (ICU categories together, congestive heart failure, cancer, orthopedic, and all other), age, activities of daily living, exercise capacity, chart documentation of weight loss, and global quality of life. The Somers' Dxy for a model including these factors was 0.48 (equivalent to a receiver-operator curve (ROC) area of 0.74, suggesting good discrimination). Bootstrap estimation indicated good model validation (corrected Dxy of 0.46, ROC of 0.73). A nomogram based on this log-normal model is presented to facilitate calculation of median survival time and 10th and 90th percentile of survival time. A count of geriatric syndromes or comorbidities did not add explanatory power to the model, nor did the hospital of patient recruitment, depression, or the patient preferences for general approach to care. The physician's perception of the patient's preferences and the physician's subjective estimate of the patient's prognosis improved the estimate of survival time significantly. CONCLUSIONS: Accurate estimation of length of life for older hospitalized persons may be calculated using a limited amount of clinical information available from the medical chart plus a brief interview with the patient or surrogate. The accuracy of this model can be improved by including measures of the physician's perception of the patient's preferences for care and the physician's subjective estimate of prognosis.

Activities of Daily Living↗
PubMed2000

Length of stay and therapeutic intervention allow estimation of in-hospital resource use independent of site and inflation.

OBJECTIVES: To develop and evaluate a model to estimate inpatient resource utilization for seriously ill patients using periodic medical record abstraction and hospital length of stay. DESIGN: A prospective cohort study of prognoses and preferences and outcomes of seriously ill hospitalized adults. The predictive model was based on the Therapeutic Intervention Scoring System (TISS), length of stay (LOS), and hospital site, and was developed on Phase I data and validated on Phase II data. SETTING: Five teaching hospitals in the United States PARTICIPANTS: The derivation sample included 4301 patients enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT). The validation sample included 4804 patients. MEASUREMENTS: Hospital charges were correlated with the product of hospital length of stay and average score from the TISS. Model fit assessment used R2 for total hospital charges. RESULTS: The correlation between hospital charges and the final model, after adjusting for site differences, was 0.86. The correlation was similar when validating the model in an independent data set. CONCLUSIONS: We present a method to estimate hospital resource utilization that is independent of site and inflation and can estimate actual costs in multiyear, multisite research endeavors.

Aged↗
PubMed2000

Compensatory sleep response to 12 h wakefulness in young and old rats.

There is a pronounced decline in sleep with age. Diminished output from the circadian oscillator, the suprachiasmatic nucleus, might play a role, because there is a decrease in the amplitude of the day-night sleep rhythm in the elderly. However, sleep is also regulated by homeostatic mechanisms that build sleep drive during wakefulness, and a decline in these mechanisms could also decrease sleep. Because this question has never been addressed in old animals, the present study examined the effects of 12 h wakefulness on compensatory sleep response in young (3.5 mo) and old (21.5 mo) Sprague-Dawley and F344 rats. Old rats in both strains had a diminished compensatory increase in slow-wave sleep (SWS) after 12 h of wakefulness (0700-1900, light-on period) compared with the young rats. In contrast, compensatory REM sleep rebound was unaffected by age. To assess whether the reduced SWS rebound in old rats might result from loss of neurons implicated in sleep generation, we counted the number of c-Fos immunoreactive (c-Fos-ir) cells in the ventral lateral preoptic (VLPO) area and found no differences between young and old rats. These findings indicate that old rats, similar to elderly humans, demonstrate less sleep after prolonged wakefulness. The findings also indicate that although old rats have a decline in sleep, this cannot be attributed to loss of VLPO neurons implicated in sleep.

Adaptation, Physiological↗
PubMed2000

The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss.

Because lifelong exposure to estrogen is a strong determinant of bone mass, we asked whether metabolic conversion of estrogen to either inactive or active metabolites would reflect postmenopausal bone mineral density (BMD) and rate of bone loss. Biochemical markers of inactive estrogen metabolites, urinary 2-hydroxyestrogen (2OHE1) and 2-methoxyestrogen (2MeOE1), and active metabolites, urinary 16alpha-hydroxyestrone (16alphaOHE1), estradiol (E2), and estriol (E3), were determined in 71 untreated, healthy postmenopausal women (age, 47-59 years) followed prospectively for 1 year. Urinary 2MeOE1 was correlated negatively with baseline vertebral (anteroposterior [AP] projection, r = -0.23 andp < 0.05; lateral view, r = -0.27 and p < 0.05) and proximal femur bone density measured by dual-energy X-ray absorptiometry (DXA; total, r = -0.38 and p < 0.01; neck, r = -0.28 and p = 0.02; trochanter, r = -0.44 and p < 0.01). BMDs of women in the lowest quartile of urinary 2MeOE1 (< 15 ng/g) were significantly higher than those in the highest quartile at all skeletal sites (p < 0.05). Likewise, women in the lowest quartile of urinary 2OHE1/16alphaOHE1 ratio (< 1.6) did not experience bone loss after 1 year, in contrast to women in the higher quartiles. We propose that the rate of inactivation of estrogens through 2-hydroxylation may contribute to postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed2000

Pollen viability reduction as a potential cost of ant association for Acacia constricta (Fabaceae).

Field studies investigating the impact of ants on the reproduction of plants bearing extrafloral nectaries have traditionally focused on seed production, a component of female fitness. The purpose of this study was to test whether ants can affect the pollen viability, a component of male fitness, when they visit flowers of the shrub Acacia constricta. Acacia constricta inflorescences hand-pollinated with flowers over which Formica perpilosa ants had crawled set significantly fewer seed pods than inflorescences hand-pollinated by control flowers that had no contact with ants. Many ant species secrete antibiotic substances onto the integument that render pollen inviable, and these secretions are probably the mechanism for reduced pollen viability in this study. The ratio of seed pods produced by self-pollinated inflorescences to those produced by cross-pollinated inflorescences was 0.16, indicating that A. constricta is largely self-incompatible. Because F. perpilosa workers forage primarily on the acacia tree under which they nest, they are unlikely to serve as efficient vectors of outcrossing. Previous work showed that A. constricta shrubs with F. perpilosa ants produce approximately twice as many seeds as similarly sized plants not so associated. The results indicate that association with F. perpilosa could cause a reproductive trade-off for A. constricta: benefits to female function may be accompanied by costs to male function. Selection to discourage ant visitation to flowers may have affected the pollination biology of this and other ant-associated plant species.

Journal Article↗
PubMed2000

Mechanisms of Mycobacterium avium pathogenesis.

Infections caused by Mycobacterium avium are common in AIDS patients and patients with chronic lung diseases. The bacterium can be acquired both through the intestinal route and respiratory route. M. avium is capable of invading mucosal epithelial cells and translocating across the mucosa. The bacterium can infect macrophages, interfering with several functions of the host cell. The host defense against M. avium is primarily dependent on CD4+ T lymphocytes and natural killer cells. Activated macrophages can inhibit or kill intracellular bacteria by mechanisms that are currently unknown, but M. avium can invade resting macrophages and suppress key aspects of their function by triggering the release of transforming growth factor beta and interleukin 10. Co-infection with HIV-1 appears to be mutually beneficial, with both organisms growing faster.

AIDS-Related Opportunistic Infections↗
PubMed2000

Distribution of hypocretin-containing neurons in the lateral hypothalamus and C-fos-immunoreactive neurons in the VLPO.

The present study investigated the distribution of neurons implicated in the regulation of sleep in three species generally used in sleep research, i.e., mice, rats and cats. We focused on sleep active neurons in the ventral lateral preoptic (VLPO) area and the hypocretin/orexin-containing neurons in the lateral hypothalamus. The latter groups of neurons were found recently to play an important role in the regulation of REM sleep. The expression of the transcription factor, c-Fos, was used to identify the VLPO. In mice and rats, in response to sleep, a discrete cluster of c-Fos positive cells was found in the VLPO. In mice, this cluster was located more medially compared to the rat, and as in the rat, galanin immunostained neurons were found in the VLPO. In the cat, c-Fos positive cells did not segregate to a specific location but were more diffusely represented in the preoptic area. In all three species, orexin/hypocretin-containing neurons were located only in the lateral hypothalamus with the distribution being more diffuse in the cat. The grouping of sleep-active cells in rodents makes it feasible to extract these cells for tissue culture and molecular analysis. Moreover, given that rodents have a distinct circadian distribution of sleep-wakefulness, the connectivity with the suprachiasmatic nucleus can also be determined.

Animals↗
PubMed1999

Transcriptional activation of APETALA1 by LEAFY.

Plants produce new appendages reiteratively from groups of stem cells called shoot apical meristems. LEAFY (LFY) and APETALA1 (AP1) are pivotal for the switch to the reproductive phase, where instead of leaves the shoot apical meristem produces flowers. Use of steroid-inducible activation of LFY demonstrated that early expression of AP1 is a result of transcriptional induction by LFY. This AP1 induction is independent of protein synthesis and occurs specifically in the tissues and at the developmental stage in which floral fate is assumed. Later expression of AP1 appears to be only indirectly affected by LFY.

Arabidopsis↗