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Biomedical subjects

M Fluri

Publications and source records attributed to M Fluri.

16 recordsLinked to original sources

The impact of automatic threshold tracking on pulse generator longevity in patients with different chronic stimulation thresholds.

Automatic adjustment of the stimulation output of pacemakers to changing stimulation thresholds using the Autocapture feature increases patient safety and decreases energy consumption. This study examined the impact of Autocapture on pulse generator longevity in patients with different chronic stimulation thresholds. Eighty patients (mean age 79 +/- 9 years; 37 men, 43 women) with Pacesetter Regency SR+ pacemakers were included in the study. Data were collected before discharge of the patients from the hospital, 6-12 weeks postimplant, and then every 6-12 months. Pulse generator longevity was calculated theoretically, assuming 100% stimulation with a stable threshold, at a pacing rate of 65 +/- 6 beats/min and 1% backup pulses. Theoretical pulse generator longevity was calculated for low (< 1 V), intermediate (> or = 1 V and < 2 V), and high (> or = 2 V) stimulation thresholds. Pulse generator longevity was compared among three groups: (A) Autocapture programmed On, (B) Autocapture programmed Off, (C) theoretical calculations using thresholds of patients in group A with the stimulation voltage programmed at twice pacing threshold, or at a minimum of 2.4 V. The mean follow-up time since implantation was 19 +/- 8 months. The calculated longevity benefits for patients in group A were 36%, 59%, and 30% compared to group B, and 19%, 32%, and 49% compared to group C in patients with low, intermediate, and high chronic stimulation thresholds, respectively. Theoretical calculations based on chronic stimulation thresholds in our patient population with Regency SR+ pacemakers suggest that Autocapture may markedly prolong pulse generator longevity in patients with a broad range of long-term pacing thresholds.

Aged↗

Midazolam premedication improves tolerance of transesophageal echocardiography.

Patient premedication for transesophageal echocardiography (TEE) is still under debate, especially the use of sedatives. We performed a double-blind, placebo-controlled study to clarify the efficacy of low-dose intravenous midazolam as premedication for TEE. Placebo or midazolam (< or =50 kg, 2.0 mg intravenously; 50 to 80 kg, 2.5 mg; and > or =80 kg, 3.0 mg intravenously) was given in addition to topical anesthesia to 200 consecutive in- and outpatients. Blood pressure, heart rate, and oxygen saturation were monitored. Patients were interviewed immediately, and 2 to 10 days after TEE. Sixteen patients received an additional dose of midazolam, and in 12 follow-up was incomplete. Patients taking midazolam reported less gag reflex at probe introduction and during TEE, as did the examiners (p < 0.05 to 0.0001). Probe manipulations were found to produce less discomfort after midazolam administration (p < 0.005). Midazolam patients experienced less dyspnea (p < 0.01) despite a minimal decrease in oxygen saturation of 2% (p < 0.0001). The following day patients taking midazolam reported less sore throats, and painful swallowing was less frequent (p < 0.01 to 0.001). Systolic blood pressure decreased slightly in the midazolam group (132 +/- 24 to 121 +/- 20 mm Hg, p < 0.0001). The rate of minor complications showed no difference. Thus, TEE probe introduction and manipulation was tolerated better after low-dose midazolam premedication, and patients experienced less pharyngeal discomfort the day after. Midazolam was well tolerated and the complication rate did not increase. Thus low-dose, short-acting benzodiazepine premedication improves patient comfort during and after TEE and generous use can be recommended.

Anesthetics, Intravenous↗

Identification and analysis of the chicken CD3epsilon gene.

The chicken T cell receptor CD3epsilon gene was isolated using a degenerate polymerase chain reaction. The 1883 bp long cDNA encoded a transmembrane protein of 16.9 kDa lacking N-linked glycosylation sites. Comparison of the chicken and mammalian CD3epsilon proteins revealed low homology in the extracellular domain with clusters of similarities located around the N-terminal cysteine residue and proximal to the transmembrane region. The high conservation of the cytoplasmic domain included motifs important for signal transduction. The alignment of all CD3gamma, CD3delta and CD3epsilon proteins allowed the identification of highly conserved residues and motifs. Southern blot analysis indicated the presence of a single copy CD3epsilon gene. The expression of the CD3epsilon transcript was limited to T cells and natural killer cells. A recessive mutation of the CD3epsilon gene in the CB chicken strain enabled the mapping of the epitope recognized by the CT3 monoclonal antibody. This analysis of the first non-mammalian CD3epsilon gene provides novel information about evolutionary conserved structural features and its expression in natural killer cells.

Amino Acid Sequence↗

[Catheter closure in atrial septal defects and open foramen ovale using the Sideris buttoned device].

Percutaneous nonsurgical closure is an alternative to surgical repair of a significant atrial septal defect (ASD) or a patent foramen ovale (PFO) associated with systemic embolism without other cause. We report the results of the first 35 patients (19 ASDs, 16 PFOs) in whom transcatheter closure was attempted. Diagnosis and follow-up were based on transesophageal echocardiography in the majority of cases. In all patients the "Sideris buttoned device" was used. A total of 19 patients (13 women) were treated for symptomatic ASD of the secundum type. The mean defect size before the intervention was 17 mm by echocardiography and 24 mm measured by balloon in the catheterization laboratory (stretched diameter) with a reduction to 4 mm after treatment measured by echocardiography. A total of 16 patients (5 women) underwent transcatheter closure of a PFO; 14 patients had had cerebral embolic events and 2 peripheral. During follow-up of 104 patient months, only one patient had a recurrent embolic event. He had at that time no occluder protecting the PFO after early embolization and extraction of the device.

Adolescent↗

c-Myc overexpression associated DHFR gene amplification in hamster, rat, mouse and human cell lines.

We have analysed relative DHFR gene copy numbers in nine cell lines of various cell type and species origins. The cells studied expressed either low, low and inducible or constitutively elevated levels of c-Myc protein. DHFR gene amplification was observed only when c-Myc protein levels were upregulated. The amplification of the DHFR gene was transient in inducible cell lines. Cell lines exhibiting constitutively deregulated c-Myc protein levels, however, showed both DHFR gene amplification and ongoing rearrangements of the DHFR locus. In contrast, the relative gene copy numbers of ribonucleotide reductase R1 subunit, ornithine decarboxylase, syndecan 2, glyceraldehyde-3-phosphate-dehydrogenase, and cyclin C remained unaffected irrespective of c-Myc protein levels, suggesting a locus-specific genomic instability of the DHFR gene in cells with deregulated c-Myc protein levels. Overall, the results of the present study support the notion that DHFR gene amplification as a consequence of c-Myc deregulation may occur in a variety of cell lines irrespective of their cell type and species origins.

Animals↗

Genomic instability in MycER-activated Rat1A-MycER cells.

The deregulated expression of c-Myc protein is associated with the non-random locus-specific amplification of the dihydrofolate reductase (DHFR) gene. This study was performed to determine whether additional chromosomal aberrations occur when c-Myc protein levels are up-regulated for prolonged periods. To this end, we have used Rat1A-MycER cells, which allow the experimental regulation of Myc protein levels. We examined the genomic stability of Rat1A-MycER cells cultivated in either the absence or the presence of estrogen, which reportedly activates the chimeric MycER protein in these cells. Following prolonged periods of MycER activation, Rat1A-Mycer cells exhibited irreversible chromosomal aberrations. The aberrations included numerical changes, chromosome breakage, the formation of circular chromosomal structures, chromosome fusions, and extrachromosomal elements.

Animals↗

High dose dipyridamole as a pharmacological stress test during cardiac catheterisation in patients with coronary artery disease.

AIM: To validate dipyridamole as a pharmacological stress test during cardiac catheterisation, allowing both functional and morphological estimation of stenosis severity. METHODS: The study encompassed 74 patients: 62 patients with significant coronary artery disease (age 61 (SD 8) years; seven women, 55 men) and 12 controls. Regional wall motion, left ventricular ejection fraction and end diastolic pressure were analysed in the resting state and after high dose intravenous dipyridamole. Patients were subdivided into four groups: group I (n = 32, 43%) had stopped all anti-ischaemic treatment for > 24 h, group II (n = 14, 19%) was under treatment, group III (n = 16, 22%) had significant coronary artery disease only in regions with regional wall motion abnormalities at rest, and group IV consisted of 12 control patients (16%) with no significant coronary artery disease (age 62 (8) years, three women, nine men). RESULTS: The sensitivity of dipyridamole testing in patients with coronary artery disease was poor. The best sensitivity was obtained with regional wall motion analysis (26/62 = 42%) and with global left ventricular ejection fraction (25/62 = 40%). Specificity was 100% for regional wall motion and 100% for ejection fraction. Calculated positive and negative predictive values for regional wall motion were 100% and 63%, respectively. CONCLUSIONS: Although safe, handy, and inexpensive, dipyridamole is not an adequate pharmacological stress test during cardiac catheterisation because of its low sensitivity.

Cardiac Catheterization↗

Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. A pilot study.

OBJECTIVES: To assess the cardioprotective efficiency of an antioxidant regimen (vitamins E, C and N-acetylcysteine) in patients receiving high dose chemo- and/or radiotherapy for malignant disease. METHODS: Prospective, placebo controlled, randomized and double blinded pilot study involving 13 patients receiving chemotherapy and 12 patients receiving radiotherapy. RESULTS: In patients receiving antioxidants, left ventricular ejection fraction did not change (63 +/- 4% to 63 +/- 4%). In the placebo group, ejection fraction changed from 67 +/- 6% to 61 +/- 4% (p = 0.03). No patient in the antioxidant group and 6/13 (46%) patients in the placebo group showed a fall of > 10% in the left ventricular ejection fraction. In the chemotherapy group, the left ventricular ejection fraction changed from 62% (+/- 2) to 63% (+/- 2) in the patients treated with antioxidants (ns) and from 63% (+/- 5) to 61% (+/- 5) in patients treated with placebo (ns). No patient showed a significant fall in ejection fraction in the antioxidant group, whereas 2/7 (29%) in the placebo group showed a reduction > or = 10%. In the radiotherapy group, left ventricular ejection fraction did not change ¿64% (+/- 6) to 64% (+/- 5)¿ in patients treated with antioxidants (ns) and changed from 70% (+/- 8) to 60% (+/- 4) in patients treated with placebo (p = 0.008). No patient in the antioxidant group, but 4/6 (66%) patients in the placebo group showed a fall of > or = 10% in ejection fraction. CONCLUSION: The small number of patients in the study precludes a definitive statement. The preliminary results however suggest efficient cardioprotection by this nontoxic and inexpensive antioxidant combination, so larger studies are warranted for confirmation.

Acetylcysteine↗

Regional wall motion changes with dobutamine as a pharmacological stress test during cardiac catheterization in patients with significant coronary artery disease.

BACKGROUND: Preliminary study to test the feasibility of pharmacological stress testing during cardiac catheterization, thus combining anatomical and functional information. PATIENTS AND METHODS: 21 consecutive patients with known or suspected coronary artery disease, referred for diagnostic catheterization. Biplane ventriculography was performed before and during dobutamine infusion. The patients were subdivided into 3 groups: Group I (n = 11, 52%) with at least one territory supplied by a significantly stenosed coronary artery and showing normal resting regional wall motion. Group II (n = 6, 29%) patients in whom the affected vessel(s) supplied exclusively a territory with regional wall motion abnormalities at rest. Group III (n = 4, 19%) had no significant coronary artery disease and served as control. RESULTS: In group I, 9/11 (82%) patients and in group II, 3/6 (50%) patients showed either ischemia or viability reactions or both after dobutamine stress. Overall, substantial functional information was gathered in 12/17 patients (71%). Control patients showed no worsening of regional wall motion under dobutamine. Neither global left ventricular ejection fraction nor left ventricular end diastolic pressure were as accurate in detecting ischemia as regional wall motion analysis. In patients who had only ischemia and no viability reaction as judged by regional wall motion analysis, ejection fraction fell significantly in 4/6 (67%) patients; end diastolic pressure on the other hand rose significantly in 3/6 (50%). CONCLUSIONS: Dobutamine stress testing performed during cardiac catheterization is convenient, feasible and safe and yields clinically useful information in a high percentage (71%) of patients with significant coronary artery disease. Further experience is needed to evaluate the sensitivity, specificity and predictive value of this new approach.

Cardiac Catheterization↗

[Cardioprotection in chemo- and radiotherapy for malignant diseases--an echocardiographic pilot study].

AIM: Pilot study, examining the cardioprotective effect of an antioxidant regimen in patients with malignancies receiving high dose chemo- or radiotherapy. PATIENTS AND METHODS: 14 patients with chemotherapy and 10 patients with radiotherapy were randomized in a double-blind fashion (placebo versus vitamin E and C and N-acetylcysteine). Systolic and diastolic echocardiographic parameters were determined before and within three weeks of treatment completion. RESULTS: Left ventricular ejection fraction fell significantly in patients receiving placebo (radiotherapy: 67 +/- 6 to 56 +/- 2%, p = 0.008, chemotherapy: 67 +/- 7 to 60 +/- 8%, p = 0.05). Patients on antioxidants showed no significant fall in EF (radiotherapy: 63 +/- 8 to 61 +/- 7%, chemotherapy: 67 +/- 5 to 64 +/- 6%). CONCLUSION: The small number of patients in the study precludes a definitive statement. The preliminary results, however, suggest efficient cardioprotection by this cheap and safe antioxidant combination, so that larger studies are warranted for confirmation.

Acetylcysteine↗

[Adult patients with congenital heart diseases: Berne statistics].

Data of the 272 adult patients with congenital heart disease followed up in our department are analyzed. We emphasize the lack of reliable statistical surveys of this group of patients at the present time. The need for better intra- and interdisciplinary cooperation, specially between referring physicians and tertiary centers, is stressed.

Adult↗

[Beta blockers in stable angina pectoris].

A concise overview of the pathophysiologic mechanisms of stable angina pectoris and the attempt to deduce its rational therapy presented. The possible mode of action of are beta-adrenergic blockers and calcium entry blockers is described. It becomes evident that the results of clinical trials do not perfectly correspond to the present pathophysiological models. The pharmacological properties of beta-adrenergic blockers are summarized with regard to the therapy of stable angina pectoris. The value of a combination of beta-adrenergic blockers and calcium entry blockers in the therapy of stable angina pectoris is discussed. Finally, the prognostic importance of silent ischemia with regard to stable angina pectoris and the possible therapeutic consequences are discussed.

Adrenergic beta-Antagonists↗

Functional heterogeneity of CD4-positive T-cell subsets: the correlation between effector functions and lymphokine secretion is limited.

Several effector functions and the lymphokine secretion pattern of 30 antigen-specific CD4+ T-cell clones have been investigated. The clones were generated directly by limiting dilution cloning of nylon wool-purified T-cells obtained from KLH immunized BALB/c mice and avoiding an initial bulk culture phase. Using this approach the CD4+ T-cell clones were grouped into helper and nonhelper subsets. Among the helper subset, clones which helped B-cells for specific antibody production by either cognate or noncognate recognition were identified. Some but not all of these helper clones fitted into the Th1 and Th2 scheme, if the lymphokine secretion pattern was evaluated. Among the nonhelper subset CD4+ clones which killed activated APC in a MHC class II-restricted and antigen-specific manner were identified. In addition, one clone which suppressed B-cell antibody production mediated by helper clones was found. However, neither the suppression of antibody responses nor the inability of the nonhelper clones to help B-cells is due to the killing of B-cells. Various attempts were made to convert nonhelper into helper clones and helper into killer clones, without success. Thus, the functional properties of these clones are stable traits and not convertible by varying the experimental conditions.

Animals↗

CD4+ T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells.

Ag-specific as well as Ia-restricted killing of certain APC by CD4+ T cells was investigated. The CD4-mediated killing is not only a characteristic of in vitro long term cultured T cell lines or clones, but is also manifest after in vivo priming. Thus, CD4+ killer T cells are generated in vivo as well. CD4+ killer T cells are detected in the Th1, but not in the Th2 subset, and they do not appear to lyse Ia+ APC or bystander cells by a pathway mediated by secreted T cell factors. The latter observation is demonstrated by cold target inhibition experiments as well as by the failure of puromycin to inhibit killing, if applied in doses which completely block lymphokine secretion. Ia+ APC differ in their susceptibility to lysis. Transformed APC are usually better lysed than nontransformed APC. Unstimulated B cells are not killed, while LPS-stimulated B cell blasts are killed. The results of cold target inhibition and bystander killing experiments suggest that CD4+ killer T cells are activated by the common pathway, i.e., by Ag presented in the context of Ia, but killing requires the recognition of additional determinant(s) on APC. It is proposed that these killing-inducing determinants are continuously expressed on most transformed Ia+ cells and on nontransformed but stimulated APC.

Animals↗

Relation between electromyogram and torque of isometric reflex contractions in man.

Human subjects maintained isometric plantar or dorsal flexions of the ankle in a matching task. H-reflexes of different sizes were superimposed on the steady activity. The peak-to-peak amplitude of the reflexes was measured on the electromyogram (EMG) of the soleus muscle. The size of the corresponding muscle contractions was determined on the isometric torque signal in relation to the maintained flexion force. The EMG-torque relation which was defined as the reflex muscle contraction as a function of the EMG reflex signal approximated a square root function for a given steady contraction level. It was not modulated by steady dorsal flexions, but it decreased continuously with stronger plantar steady torques. This dependence was caused by the silent period following the reflex discharge. Since the reflex discharge and the silent period were near in time to the duration of the contraction, the silent period had a direct effect on the reflex contraction amplitude.

Electromyography↗