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Biomedical subjects

B Meier

Publications and source records attributed to B Meier.

At least 37 records · Page 2Linked to original sources
PubMed2001

Promotion of collateral growth by granulocyte-macrophage colony-stimulating factor in patients with coronary artery disease: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimentally, activated macrophages have been documented to induce vascular proliferation. METHODS AND RESULTS: In 21 patients (age 74+/-9 years) with extensive coronary artery disease not eligible for coronary artery bypass surgery, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF, Molgramostim) on quantitatively assessed collateral flow was tested in a randomized, double-blind, placebo-controlled fashion. The study protocol consisted of an invasive collateral flow index (CFI) measurement immediately before intracoronary injection of 40 microg of GM-CSF (n=10) or placebo (n=11) and after a 2-week period with subcutaneous GM-CSF (10 microg/kg) or placebo, respectively. CFI was determined by simultaneous measurement of mean aortic pressure (P(ao), mm Hg), distal coronary occlusive pressure (P(occl), mm Hg; using intracoronary sensor guidewires), and central venous pressure (CVP, mm Hg): CFI=(P(occl)-CVP)/(P(ao)-CVP). CFI, expressing collateral flow during coronary occlusion relative to normal antegrade flow during vessel patency, changed from 0.21+/-0.14 to 0.31+/-0.23 in the GM-CSF group (P<0.05) and from 0.30+/-0.16 to 0.23+/-0.11 in the placebo group (P=NS). The treatment-induced difference in CFI was +0.11+/-0.12 in the GM-CSF group and -0.07+/-0.12 in the placebo group (P=0.01). ECG signs of myocardial ischemia during coronary balloon occlusion occurred in 9 of 10 patients before and 5 of 10 patients after GM-CSF treatment (P=0.04), whereas they were observed in 5 of 11 patients before and 8 of 11 patients after placebo (P=NS). CONCLUSIONS: This first clinical study investigating the potential of GM-CSF to improve collateral flow in patients with coronary artery disease documents its efficacy in a short-term administration protocol.

Aged↗
PubMed2001

Prognosis after percutaneous closure of patent foramen ovale for paradoxical embolism.

The long-term risk and risk factors for recurrent embolism after percutaneous closure of patent foramen ovale (PFO) were investigated in 152 consecutive patients with presumed paradoxical embolism. During follow-up, the actuarial freedom from recurrent embolism was 95.1% at 1 year, and 90.6% at 2 and 6 years. A residual shunt after percutaneous PFO closure was a predictor for recurrence (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02). Randomized trials comparing medical treatment with percutaneous PFO closure in the prevention of recurrent embolism are in progress.

Adult↗
PubMed2001

Stent coating with titanium-nitride-oxide for reduction of neointimal hyperplasia.

BACKGROUND: Coronary stents prevent constrictive arterial remodeling but stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body reaction, which is absent for titanium. The hypothesis of the present study was that titanium renders the stent surface biologically inert, with reduced platelet and fibrinogen binding. METHODS AND RESULTS: Twelve pigs were instrumented with a stainless steel and 2 titanium-nitride-oxide-coated stents (TiNOX 1, ceramic; TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens of stented segments were analyzed by digital morphometry. Platelet adhesion and fibrinogen binding studies were performed in the perfusion chamber. Under in vitro conditions, TiNOX 1 showed reduced platelet adhesion (65+/-3%) compared with TiNOX 2 (72+/-5%; P<0.05) and stainless steel (71+/-4%; P<0.05). Platelet adhesion 48 hours after incubation with human plasma, however, was not different between TiNOX 1 (17+/-3%) and 2 (15+/-3%) but was significantly higher with stainless steel (23+/-2%; P<0.05). Fibrinogen binding was significantly reduced with TiNOX 2 (54+/-3%) compared with TiNOX 1 (82+/-4%, P<0.05) or stainless steel (100%, P<0.05). Histomorphometry revealed a significantly larger neointimal area in stainless steel (2.61+/-1.12 mm(2)) than in TiNOX 1-coated (1.47+/-0.84 mm(2), P<0.02) or TiNOX 2-coated (1.39+/-0.93 mm(2), P<0.02) stents. The reductions were 44% and 47%, respectively. CONCLUSIONS: TiNOX coating significantly reduces neointimal hyperplasia in stainless steel stents. The antiproliferative effect was similar for both TiNOX coatings, suggesting that the electrochemical properties are more important for attenuation of neointimal proliferation than the observed differences in platelet adhesion and fibrinogen binding.

Alloys↗
PubMed2001

Sympathetic stimulation using the cold pressor test increases coronary collateral flow.

BACKGROUND: Little is known about the vasomotor function of human coronary collateral vessels. The purpose of this study was to examine collateral flow under a strong sympathetic stimulus (cold pressor test, CPT). METHODS: In 30 patients (62 +/- 12 years) with coronary artery disease, two subsequent coronary artery occlusions were performed with random CPT during one of them. Two minutes before and during the 1 minute-occlusion, the patient's hand was immerged in ice water. For the calculation of a perfusion pressure-independent collateral flow index (CFI), the aortic (Pao), the central venous (CVP) and the coronary wedge pressure (Poccl) were measured: CFI = (Poccl - CVP)/(Pao - CVP). RESULTS: CPT lead to an increase in Pao from 98 +/- 14 to 105 +/- 15 mm Hg (p = 0.002). Without and with CPT, CFI increased during occlusion from 14% +/- 10% to 16% +/- 10% (p = 0.03) and from 17% +/- 9% to 19% +/- 9% (p = 0.006), respectively, relative to normal flow. During CPT, CFI was significantly higher at the beginning as well as at the end of the occlusion compared to identical instants without CPT. CFI at the end of the control occlusion did not differ significantly from the CFI at the beginning of occlusion with CPT. CONCLUSIONS: During balloon occlusion, collateral flow increased due to collateral recruitment independent of external sympathetic stimulation. Sympathetic stimulation using CPT additionally augmented collateral flow. The collateral-flow-increasing effect of CPT is comparable to the recruitment effect of the occlusion itself. This may reflect a coronary collateral vasodilation mediated by the sympathetic nervous system.

Aged↗
PubMed2001

[Referral pattern of the heart catheterization laboratory at the Bern Island University Hospital].

Coronary angiography is a common diagnostic procedure to identify patients with coronary artery disease who need to undergo revascularization. It is expensive, carries a certain risk and must therefore be thoroughly scrutinized. An expert panel evaluated the indication criteria (Swiss Guidelines) to serve as a decision basis for the work-up of patients. The presented data acquisition considers the pathway of assignment as well as demographic data in addition to these criteria. A total of 2369 patients were referred to the cardiac catheterization laboratory of the University Hospital of Berne in 1996. Of these, 504 (21%) were randomly analyzed retrospectively. The selection consisted of the first 84 patients every second month. For 90% of these patients, the Swiss Guidelines attested an appropriate indication. The majority of the remaining 10% of the patients showed an appropriate indication as well which, however, had not been included into the Swiss Guidelines. Compared with other studies it is of note that one third of the patients underwent no prior stress test. In contrast, in a similar study in Frankfurt three quarters of the patients had a stress test to assess the chest pain before angiography. An increased percentage of patients with a previous coronary angioplasty was found in Berne. It may reflect the more recent period of data collection. The data represent a valid impression of the patient mix of the cardiac catheterization laboratory at the University Hospital of Berne. The indications for coronary angiography were found to be appropriate in virtually all cases. Demographic variables and procedure results are in keeping with comparable studies.

Adult↗
PubMed2001

ABC stenosis morphology classification and outcome of coronary angioplasty: reassessment with computing techniques.

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification (MC) stratifies coronary lesions for probability of success and complications after coronary angioplasty (PTCA). Modern computing techniques were used to evaluate the individual predictive value of MC in random PTCA cases. METHODS AND RESULTS: MC was attributed to the target lesions by consensus of 2 observers. The predictive value regarding procedural success (PS) and major adverse cardiac events (MACE) of MC was analyzed by conventional logistic regression analyses and by inductive machine learning models. The study was adequately powered for the methods applied with 325 target lesions of 250 cases. Overall, PS decreased and MACE increased from type A to type C lesions. Regression analysis identified no single factor as predictive. Logistic regression showed an error rate of 42%. Machine learning techniques achieved an individual predictive error of only 10%, which could be further reduced to 2% by addition of parameters. For PS, MC parameters showed a high ranking for building the model. For MACE, variables of the medical history showed more impact. CONCLUSIONS: MC per se cannot individually predict PS or MACE. However, when all MC parameters are integrated together with additional lesion-specific and history variables, a high individual predictive value can be achieved. This technique may be clinically helpful for risk stratification in the catheterization laboratory and improvement of classification systems in interventional cardiology.

Algorithms↗
PubMed2001

Collateral and collateral-adjacent hyperemic vascular resistance changes and the ipsilateral coronary flow reserve. Documentation of a mechanism causing coronary steal in patients with coronary artery disease.

OBJECTIVES: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. METHODS: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (P(occl), using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (P(ao)), a collateral flow index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (R(ipsi), R(coll), R(contra)) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI> or =0.15. RESULTS: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78+/-10% versus 82+/-12% (NS). CFVR was not associated with %-S. In the group with CFI> or =0.15 but not with CFI<0.15, CFVR was directly and inversely associated with R(coll) and R(contra), respectively. CONCLUSIONS: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below 1.

Adenosine↗
PubMed2001

Combined percutaneous pulmonary valvuloplasty and atrial septal defect closure for pulmonary valvular stenosis and associated secundum atrial septal defect in an adult.

Percutaneous balloon valvuloplasty is the treatment of choice for congenital pulmonary valve stenosis, and percutaneous closure of secundum atrial septal defects has become a promising alternative to surgery in selected patients. We report a case of combined percutaneous pulmonary valvuloplasty and secundum atrial septal defect occlusion in an adult patient.

Adult↗
PubMed2001

Reactive oxygen intermediates involved in cellular regulation.

Reactive oxygen intermediates (ROIs) in low concentration, as released permanently by nonphagocytic cells, possess important functions in inter- and intracellular signalling. They lead to alterations in the phosphorylation pattern followed by gene activation, including the expression of proto-oncogenes. Redox-sensitive sites in membrane molecules may trigger adhesion and chemotaxis or open ion channels and activate transport processes across the cytoplasma membrane. ROIs shift the ratio of cyclic GMP to cyclic AMP giving signals to proliferation and differentiation processes. Senescence, apoptosis, and cell death can also be modulated by ROIs, depending on concentration and cell type.

Animals↗
PubMed2001

Superoxide generation of phagocytes and nonphagocytic cells.

Phagocytes release high amounts of reactive oxygen intermediates upon contact with appropriate stimuli into the environment as an important function in the immune defence against infectious agents. On the other hand nonphagocytic cells release low amounts upon stimulation, which have important functions in the inter- and intracellular signal transduction. Both systems represent a class of isoenzymes making a specific regulation possible. Fibroblasts, hepatocytes, and HeLa cells possess a superoxide system which shows higher activity with NADH than NADPH. The enzyme was purified to homogeneity in an active form, showed a molecular mass of 84 kDa and possessed a flavin and low-potential cytochrome b558.

Animals↗
PubMed2001

[Expression of lectin binding sites as a prognostic parameter in mouth mucosa carcinomas].

BACKGROUND: Normal oral mucosa and invasive squamous cell carcinoma of the oral mucosa and the lips were examined immunoenzymatically for different lectin-binding sites and evaluated semiquantitatively. In 110 patients suffering from invasive squamous cell carcinoma of the oral mucosa or the lips, the course of the disease was examined retrospectively with regard to metastases, recurrence and survival time over a minimum of 60 months and was correlated with cell surface binding to lectins (PNA, WGA, UEA I) of the primary tumor. Normal oral mucosa shows intensive cell surface binding to the lectins PNA, WGA and UEA I, but in more than half of the cases the PNA-defined epitopes are blocked by sialic acid. RESULTS: The comparison of the cumulated survival rates showed a much better prognosis for primary tumors with lectin-binding sites than for those without. Strong and medium WGA-binding pT2 tumors showed significantly better survival rates than those pT2 tumors with poor WGA-binding sites. Carcinomas without lectin binding showed the highest recurrence risk in the course of the disease. In squamous cell carcinomas without WGA and UEA I bindings, the period of time before a relapse occurred was significantly shortened. Carcinomas expressing UEA I-binding sites showed a considerably lower metastasis rate than UEA I-negative tumors. Squamous cell carcinomas with complete sialic acid-blocked PNA-binding sites had the same lymph node metastasis rate as those without expression of PNA-specific disaccharides. A significantly lower metastasis rate than both these groups was exhibited by tumors without or with only partially blocked PNA-binding sites. DISCUSSION: In addition to aiding routine grading, the study of PNA-, WGA- and UEA I-binding patterns can therefore provide further information in cases of oral squamous cell carcinoma regarding the potential for metastasis and tumor prognosis.

Adult↗
PubMed2001

Do beta-adrenergic blocking agents increase coronary flow reserve?

BACKGROUND: Beta-adrenergic blocking agents are the cornerstone in the treatment of coronary artery disease (CAD). The exact pathophysiologic mechanism is not clear but depends largely on the oxygen-sparing effect of the drug. Thus, the effect of metoprolol on coronary flow reserve and coronary flow velocity reserve (CFVR) was determined in patients with CAD. METHODS: Coronary blood flow velocity was measured with the Doppler flow wire in 23 patients (age: 56 +/- 10) undergoing percutaneous transluminal coronary angioplasty for therapeutic reasons. Measurements were carried out at rest, after 1-min vessel occlusion (postischemic CFVR) as well as after intracoronary adenosine (pharmacologic CFVR) before and after 5 mg intravenous metoprolol. In a subgroup (n = 15), absolute flow was measured from coronary flow velocity multiplied by coronary cross-sectional area. RESULTS: Rate-pressure product decreased after metoprolol from 9.1 to 8.0 x 10(3) mm Hg/min (p < 0.001). Pharmacologic CFVR was 2.1 at rest and increased after metoprolol to 2.7 (p = 0.002). Likewise, postischemic CFVR increased from 2.6 to 3.3 (p < 0.001). Postischemic CFVR was significantly higher than pharmacologic CFVR before as well as after metoprolol. Coronary vascular resistance decreased after metoprolol from 3.4 +/- 2.0 to 2.3 +/- 0.7 mm Hg x s/cm (p < 0.02). CONCLUSIONS: The following conclusions were drawn from this study. Metoprolol is associated with a significant increase in postischemic and pharmacologic CFVR. However, postischemic CFVR is significantly higher than pharmacologic CFVR. The increase in CFVR by metoprolol can be explained by a reduction in vascular resistance. The increase in CFVR (= increased supply) and the reduction in oxygen consumption (= decreased demand) after metoprolol explain the beneficial effect of this beta-blocker in patients with CAD.

Adrenergic beta-Antagonists↗
PubMed2001

Frequency distribution of collateral flow and factors influencing collateral channel development. Functional collateral channel measurement in 450 patients with coronary artery disease.

OBJECTIVES: We sought to determine the pathogenetic predictors of collateral channels in a large cohort of patients with coronary artery disease (CAD). BACKGROUND: The frequency distribution of collateral flow in patients with CAD is unknown. Only small qualitative studies have investigated which factors influence the development of collateral channels. METHODS: In 450 patients with one- to three-vessel CAD undergoing percutaneous transluminal coronary angioplasty (PTCA), collateral flow was measured. A collateral flow index (CFI; no unit) expressing collateral flow relative to normal anterograde flow was determined using coronary wedge pressure or Doppler measurements through sensor-tipped PTCA guide wires. Frequency distribution analysis of CFI and univariate and multivariate analyses of 32 factors, including gender, age, patient history, cardiovascular risk factors, medication and coronary angiographic data, were performed. RESULTS: Two-thirds of the patients had a CFI < 0.25 and approximately 40% of patients had a CFI < 0.15, but only approximately 10% of the patients had a recruitable CFI > or =0.4. By univariate analysis, the following were predictors of CFI > or =0.25: high levels of high-density lipoprotein cholesterol, the absence of previous non-Q-wave myocardial infarction, angina pectoris during an exercise test, angiographic indicators of severe CAD and the left circumflex or right coronary artery as the collateral-receiving vessel. Percent diameter stenosis of the lesion undergoing PTCA was the only independent predictor of a high CFI. CONCLUSIONS: This large clinical study of patients with CAD in whom collateral flow was quantitatively assessed reveals that two-thirds of the patients do not have enough collateral flow to prevent myocardial ischemia during coronary occlusion, and that coronary lesion severity is the only independent pathogenetic variable related to collateral flow.

Aged↗
PubMed2001

TNF-alpha dependent NF-kappa B activation in cultured canine keratinocytes is partly mediated by reactive oxygen species.

The cytokine TNF-alpha plays a major role in inflammatory and immunological reactions of canine skin. With respect to a possible therapeutic modulation, we investigated the role of the transcription factor NF-kappa B and the involvement of reactive oxygen species (ROS) in the TNF-alpha signalling pathway in cultured canine keratinocytes. TNF-alpha treatment resulted in activation of NF-kappa B which was partially inhibited by the antioxidant alpha-lipoic acid. Using the cytochrome c reduction test no superoxide production could be detected in the supernatant of TNF-alpha stimulated keratinocytes. However, TNF-alpha dependent intracellular hydrogen peroxide production was demonstrated spectroscopically. With electron energy loss spectroscopy (EELS) significant hydrogen peroxide formation was detected in the mitochondria, the endoplasmic reticulum, the cytosol and partially on the plasma membrane of the keratinocytes. Hence, ROS possibly play an important role in the TNF-alpha signalling pathway leading to NF-kappa B activation in canine skin. An adjunctive therapy with natural potent antioxidants modulating NF-kappa B overactivation in canine cutaneous inflammation may be of therapeutic benefit.

Animals↗