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Biomedical subjects

Michael Pfeifer

Publications and source records attributed to Michael Pfeifer.

31 records · Page 2Linked to original sources
PubMed2004

Effects of a new spinal orthosis on posture, trunk strength, and quality of life in women with postmenopausal osteoporosis: a randomized trial.

OBJECTIVE: One fourth of women > or =50 yrs of age in the general population have one or more vertebral fractures. The orthotic treatment modality in the management of vertebral fractures caused by osteoporosis remains subjective because no objective data from clinical trials are available. The objective of this research was to evaluate the efficacy of a newly developed spinal orthosis in patients with osteoporotic vertebral fractures. DESIGN: We conducted a study that measured trunk muscle strength, angle of kyphosis, body height, body sway, and variables of quality of life such as pain, well-being, and limitations of daily living. RESULTS: Wearing the orthosis for 6-mo period was associated with a 73% increase in back extensor strength, a 58% increase in abdominal flexor strength, an 11% decrease in angle of kyphosis, a 25% decrease in body sway, a 7% increase in vital capacity, a 38% decrease in average pain, a 15% increase in well-being, and a 27% decrease in limitations of daily living. The overall tolerability of the orthosis was good, no side-effects were reported, and the drop-out rate of 3% was rather low. CONCLUSIONS: The use of an orthosis increases trunk muscle strength and thus improves posture in patients with vertebral fractures caused by osteoporosis. In addition, a better quality of life is achieved by pain reduction, decreased limitations of daily living, and improved well-being. Therefore, the use of an orthosis may represent an efficacious nonpharmacologic treatment option for spinal osteoporosis.

Aged↗
PubMed2004

Activation of bronchial epithelial cells in smokers without airway obstruction and patients with COPD.

STUDY OBJECTIVE: The aim of this study was to investigate the basal level as well as the tumor necrosis factor (TNF)-alpha- and interferon (IFN)-gamma-induced expression and release of the neutrophil chemoattractants interleukin (IL)-8 and growth-related oncogene (GRO)-alpha in primary bronchial epithelial cells (PBECs) from smokers without airflow obstruction and patients with COPD. In addition, the expression of both TNF-alpha-receptor subtypes--p55 TNF-receptor subtype (TNF-R55) and p75 TNF-receptor subtype (TNF-R75)--was quantified in PBECs. DESIGN: PBECs from eight smokers without airflow limitation and eight patients with COPD were stimulated with 50 ng/mL of TNF and 200 U/mL of IFN-gamma for 4 h along with unstimulated time controls. The transcriptional expression and protein release were quantitatively assessed by means of real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Basal level messenger RNA (mRNA) expression and protein release of IL-8 and GRO-alpha were not significantly different between both groups, although a trend toward higher IL-8 levels was seen in patients with COPD. TNF-alpha induced significantly higher mRNA amounts of IL-8 (p = 0.005) and GRO-alpha (p = 0.007) in patients with COPD. This was accompanied by higher protein release data for IL-8 (p = 0.005) and GRO-alpha (p = 0.007). IFN-gamma had no significant effect on the mRNA expression and protein release of IL-8 and GRO-alpha in either group. TNF-R55 and TNF-R75 were detectable in PBECs. However, no significant differences were found between both groups with respect to steady-state mRNA levels of TNF-alpha-receptor subtypes. CONCLUSION: PBECs from patients with COPD show significantly higher TNF-alpha-induced release of the neutrophil chemoattractant CXC-chemokines IL-8 and GRO-alpha compared to smokers without airflow limitation. This increased activation of PBECs may contribute to the predominance of neutrophils seen in the airway lumen of patients with COPD.

Bronchi↗
PubMed2003

Enhanced ventilatory response to exercise in patients with chronic heart failure and central sleep apnea.

BACKGROUND: In patients with chronic heart failure (CHF), central sleep apnea (CSA) and enhanced ventilatory response (VE/VCO2 slope) to exercise are common. Both breathing disorders alone indicate poor prognosis in CHF. Although augmented chemosensitivity to CO2 is thought to be one important underlying mechanism for both breathing disorders, it is unclear whether both breathing disorders are related closely in patients with CHF. METHODS AND RESULTS: We investigated 20 CHF patients with clinically important CSA (apnea-hypopnea-index (AHI), number of episodes per hour >or=15) and 10 CHF patients without CSA. Patients with and without CSA did not differ with respect to exercise capacity (peak VO2, 63.4+/-3.4% versus 60.8+/-4.4% of predicted value; P=0.746) and left ventricular ejection fraction (LVEF, 31+/-2% versus 31+/-3%; P=0.948). The AHI was not correlated with exercise capacity (peak VO2, percent of predicted value; P=0.260) and LVEF (percent, P=0.886). In contrast, the positive correlation of the VE/VCO2 slope, determined by cardiopulmonary exercise testing, with the AHI was highly significant (P<0.001). The VE/VCO2 slope was significantly increased in patients with CSA compared with those without CSA (29.7 versus 24.9; P<0.001). CONCLUSIONS: The ventilatory response to exercise is significantly augmented in CHF patients with CSA compared with those without. In contrast to peak VO2 and LVEF, the VE/VCO2 slope is strongly related to the severity of CSA in patients with CHF, which underscores an augmented chemosensitivity to CO2 as a common underlying pathophysiological mechanism.

Chronic Disease↗
PubMed2003

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Accidental Falls↗
PubMed2003

Microsatellite instability at chromosome 8p in non-small cell lung cancer is associated with lymph node metastasis and squamous differentiation.

Genetic alterations at chromosome arm 8p are associated with advanced disease and poor patient outcome in several types of malignant tumors. We studied the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 8p in early stage non-small cell lung cancer (NSCLC) of 47 patients with stage I or II disease (25 squamous cell carcinomas and 22 adenocarcinomas). Microsatellite analysis was performed after laser microdissection using 5 polymorphic tetranucleotide microsatellite markers and 4 dinucleotide markers at chromosome 8p. A pentanucleotide repeat marker at the chromosomal locus 17p13.1 (TP53.Alu) was also analyzed. Expression of the mismatch repair (MMR) proteins hMSH2, hMSH6 and hMLH1 was evaluated by immunohistochemistry. Microsatellite instability (MSI) in at least 2 markers was detected in 9 of 47 patients (19.1%) and was predominantly found at tetranucleotide repeats. Sixteen of 47 (34.0%) NSCLC demonstrated LOH at chromosome 8p. All MSI-positive tumors showed normal expression of the MMR proteins. The presence of MSI at chromosome 8p was associated with lymph node metastasis (p=0.02), squamous differentiation (8/25; 32%-p=0.03), and the presence of LOH at the p53 locus (p=0.06). None of the other investigated clinical, pathologic or molecular factors correlated with MSI. Our study showed that an elevated MSI at selected tetranucleotide sequences (EMAST) on chromosome 8p is frequent in early stage squamous cell carcinomas of the lung with lymphatic spread. The tetranucleotide marker panel used in this study was able to indicate lymph node metastasis and high risk disease in patients with resectable squamous cell lung cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Effects of ET-A receptor blockade on eNOS gene expression in chronic hypoxic rat lungs.

We tested the hypothesis that pulmonary endothelial nitric oxide synthase (eNOS) gene expression is primarily regulated by hemodynamic factors and is thus increased in rats with chronic hypoxic pulmonary hypertension. Furthermore, we examined the role of endothelin (ET)-1 in this regulatory process, since ET-1 is able to induce eNOS via activation of the ET-B receptor. Therefore, chronic hypoxic rats (10% O(2)) were treated with the selective ET-A receptor antagonist LU-135252 (50 mg x kg(-1) x day(-1)). Right ventricular systolic pressure and cross-sectional medial vascular wall area of pulmonary arteries rose significantly, and eNOS mRNA levels increased 1.8- and 2.6-fold after 2 and 4 wk of hypoxia, respectively (each P < 0.05). Pulmonary ET-1 mRNA and ET-1 plasma levels increased significantly after 4 wk of hypoxia (each P < 0.05). LU-135252 reduced right ventricular systolic pressure, vascular remodeling, and eNOS gene expression in chronic hypoxic rats (each P < 0.05), whereas ET-1 production was not altered. We conclude that eNOS expression in chronic hypoxic rat lungs is modified predominantly by hemodynamic factors, whereas the ET-B receptor-mediated pathway and hypoxia seem to be less important.

Animals↗
PubMed2002

Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension.

OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O(2)) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-1 production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Ethnic differences in postprandial triglyceride response to a fatty meal and lipoprotein lipase in lean and obese African American and Caucasian women.

The purpose of this study was to determine if there were differences in the expression of lipoprotein lipase (LPL) in African American (AA) and Caucasian (CA) women. LPL mRNA and protein levels were determined in subcutaneous and omental fat of lean and obese subject from the 2 races (4 groups; 12 to 15 subjects/group). LPL mRNA levels of lean AA were not different from the lean CA women in either fat depot. LPL mRNA levels in the subcutaneous fat of the obese AA were higher than those of CA women (1.3 +/- 0.1 v 0.86 +/- 0.06, P.05), but not different in omental fat. LPL mass in subcutaneous fat of lean AA was higher (0.95 +/- 0.09 v 0.64 +/- 0.06, P.05), but not different in omental fat from the CA women. LPL mass in subcutaneous and omental fat was not different in the 2 obese groups. Differences in the activity of LPL were evaluated by (1) measuring the increments of triglycerides (TG) at 2, 4, 6, and 8 hours after a fat-rich meal and (2) by measuring postheparin plasma lipolytic activity. Plasma TG levels in the lean AA were lower than those of the lean CA women at basal and at 2, 4, 6, and 8 hours postprandially. The increase in TG levels at 2 hours tended to be lower in the AA than the CA women, was significantly lower at 4 hours (24 +/- 5 v 45 +/- 7, P.05), and was not different 8 hours postprandially. No differences were observed in either the absolute or the incremental concentrations of TG in the obese groups. Postheparin plasma LPL activity was higher in the lean AA than the lean CA women (4.8 +/- 0.4 v 3.4 +/- 0.4, P.05), but not different in the obese groups. These results indicate that the lower TG concentrations in the lean AA women may be partly due to enhanced expression, activity, and intravascular availability of LPL. Furthermore, it appears that the racial differences in expression and function of LPL are attenuated with obesity.

Black People↗
PubMed2002

Hemodynamic effects of aerosolized iloprost in pulmonary hypertension at rest and during exercise.

STUDY OBJECTIVES: Aerosolized iloprost, a stable prostacyclin analog, improves functional capacity even in patients with pulmonary hypertension who did not show a vigorous hemodynamic response after iloprost inhalation at rest. We therefore speculated that aerosolized iloprost elicits more beneficial effects on pulmonary hemodynamics during exercise than at rest. DESIGN AND SETTING: A prospective, open, uncontrolled study at a university hospital. PATIENTS: Sixteen patients with primary or secondary pulmonary hypertension. INTERVENTIONS: Right-heart catheterization at rest and during exercise before and after the inhalation iloprost, 14 to 28 microg. RESULTS: Before iloprost treatment, exercise increased mean (+/- SD) pulmonary artery pressure (PAPm) from 45 +/- 8 to 70 +/- 13 mm Hg, cardiac output from 3.7 +/- 1.0 to 5.8 +/- 2.4 L/min, and pulmonary vascular resistance (PVR) from 904 +/- 322 to 1,013 +/- 432 dyne.s.cm(-5) (each p < 0.05). After recovery, iloprost reduced PAPm from 44 +/- 8 to 41 +/- 6 mm Hg, increased cardiac output from 3.7 +/- 1.0 to 4.9 +/- 1.4 L/min, and lowered PVR from 902 +/- 350 to 636 +/- 248 dyne x s x cm(-5) (each p < 0.05). During exercise after iloprost, PAPm increased to 57 +/- 8 mm Hg, cardiac output to 7.0 +/- 3.0 L/min, and PVR to 673 +/- 279 dyne x s x cm(-5) (each p < 0.05 vs first exercise test). Systemic BP was not altered significantly by iloprost treatment during exercise. CONCLUSIONS: Aerosolized iloprost treatment exerts more favorable effects on pulmonary hemodynamics during exercise than at rest. These findings explain the functional improvement observed in patients with pulmonary hypertension who show only a moderate pulmonary vasodilatory response during iloprost inhalation at rest. Whether these beneficial effects have prognostic significance needs to be elucidated by further study.

Administration, Inhalation↗
PubMedDate not supplied

Expression and release of interleukin-8 by human bronchial epithelial cells from patients with chronic obstructive pulmonary disease, smokers, and never-smokers.

BACKGROUND: One of the consistently observed features in chronic obstructive pulmonary disease (COPD) are markedly increased neutrophils in the airways which are accompanied by increased levels of interleukin-8 (IL-8) in induced sputum and bronchoalveolar lavage fluid. To some extent, IL-8 may derive from bronchial epithelial cells since airway epithelium plays a crucial role in initiating and augmenting host defense mechanisms. OBJECTIVES: We hypothesized that a marked increase in bronchoepithelial IL-8 expression and release may be found in the airway epithelium of COPD patients compared to 'healthy' smokers and never-smokers. METHODS: Primary bronchoepithelial cell cultures from COPD patients, smokers, and never-smokers were established. The unstimulated and TNFalpha-induced IL-8 release was measured by enzyme-linked immunosorbent assay. In addition, mRNA expression levels were quantified by means of reverse transcriptase polymerase chain reaction and light cycler measurements. RESULTS: In subjects with COPD the constitutive and stimulated IL-8 release was significantly higher compared to 'healthy' smokers and control subjects, whereas no differences were seen between smokers and the control group. Quantitative assessment of transcript levels confirmed these data, displaying significantly higher mRNA levels in primary bronchial epithelial cells from COPD patients compared to controls (p < 0.05) in uninduced and stimulated conditions (p < 0.05). CONCLUSIONS: These results suggest that patients with chronic obstructive airflow limitation are characterized by a significant upregulation of bronchial epithelial IL-8 expression levels and secretion, indicating specific differences in epithelial cell activation in COPD patients compared to smokers and control subjects.

Epithelial Cells↗