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Biomedical subjects

J van der Linden

Publications and source records attributed to J van der Linden.

At least 19 recordsLinked to original sources
PubMed2002

Analysis of temporal requirements for myocardial tissue velocity imaging.

AIMS: Movements of myocardial walls include components of high velocity and short duration calling for a high sampling rate in the acquisition of tissue velocity imaging data. This study aims at establishing the optimal sampling requirements for tissue velocity imaging measurements. METHODS AND RESULTS: In 16 healthy individuals, tissue velocity imaging data were acquired at a frame rate of 141-203 frames/s for a subsequent off-line analysis using software enabling a reduction of the sampling rate to 50%, 25% and 12.5% of the initial frame rate. Different components of the myocardial velocity profile were measured at each of these frame rates. The deviation of the results from the initial values increased markedly at decreasing frame rates, producing an underestimation of peak systolic and diastolic velocities, most other measured parameters being overestimated. A cut-off point for an acceptable < or =10% deviation of the results corresponded to at least 70 frames/s for peak systolic and early diastolic velocity, and to at least 100 frames/s for other systolic and diastolic parameters. CONCLUSION: A high sampling rate is essential for a proper rendering of tissue velocity imaging signals, too low frame rates resulting in inferior accuracy of the results. This should be kept in mind while viewing reported tissue velocity imaging data.

Adolescent↗
PubMed2001

[Electrical conversion of atrial fibrillation. Superior effects of biphasic transthoracic method when compared with the conventional monophasic method].

Can biphasic electrical conversion of atrial fibrillation replace the standard monophasic method? This report reviews factors facilitating the electrical conversion of atrial fibrillation and describes a clinical trial, showing superior effects of biphasic versus monophasic electrical conversion of atrial fibrillation. We conclude that the most important factors for successful electrical conversion of atrial fibrillations are 1) a biphasic impulse, 2) low transthoracic impedance and 3) a short history of atrial fibrillation.

Atrial Fibrillation↗
PubMed2001

Tumor cell killing by in vitro affinity-matured recombinant human monoclonal antibodies.

We have developed a method that allows the rapid improvement of the affinity of phage-displayed antibody fragments by selection on intact eukaryotic cells. A single chain Fv fragment, specific for the tumor-associated Ep-Cam molecule, was mutagenized by shuffling of the immunoglobulin light chain variable region and DNA shuffling of both heavy and light chain variable regions. Higher-affinity mutants were selected from small phage display libraries by cell panning under stringent conditions. When converted to an intact fully human antibody, the mutagenized anti-tumor monoclonal antibody displayed an affinity of 0.4 nM, a 15-fold improvement over the affinity of the original antibody. Compared to previously reported affinity maturation schemes, panning on intact cells does not require purified targets for selection and may be particularly useful when the target molecule can not be expressed as a recombinant molecule or easily purified without disrupting its native configuration. In vitro tumor cell killing assays demonstrated an improved performance of the higher-affinity antibody in complement-mediated tumor cell killing. In contrast, the lower-affinity antibody performed somewhat better in antibody-dependent cellular cytotoxicity assays and penetrated better in multicell spheroids of tumor cells, an in vitro model for the tumor penetration capacity of antibodies.

Amino Acid Sequence↗
PubMed2001

Transaortic approach for the Alfieri stitch.

The management of associated mitral regurgitation in patients undergoing cardiac surgery is controversial. A simple, reliable, and fast repair is advantageous, especially in critically ill patients. We describe a simple method of transaortic edge-to-edge repair in patients with associated mitral regurgitation undergoing aortic valve surgery.

Aged↗
PubMed2001

Elevations in antidiuretic hormone and aldosterone as possible causes of fluid retention in the Maze procedure.

BACKGROUND: Reduced levels of atrial natriuretic peptide (ANP) has been suggested as a cause of fluid retention after combined Maze and valvular surgery. This study aimed to assess hormonal activation in the perioperative setting of isolated Maze procedures. METHODS: Changes in ANP, brain natriuretic peptide (BNP), antidiuretic hormone (ADH), aldosterone, and angiotensin II were measured in 16 patients (mean age 53+/-9 years) without concomitant heart disease undergoing the Maze (III) procedure. Ten matched patients (mean age 56+/-9 years) undergoing multivessel coronary artery bypass grafting served as controls. Measurements with hemodynamic correlates were obtained at baseline and after ventricular pacing (100 stimulations/minute), directly preoperatively, postoperatively and the first postoperative day. Weight gain and diuretic requirements were recorded. RESULTS: The major differences in hormonal response were significantly higher plasma levels of ADH (Maze preoperative 1.1+/-0.4, postoperative 24.9+/-16.7 pmol/L; controls preoperative 1.1+/-0.1, postoperative 3.7+/-3.5 pmol/L) and aldosterone (Maze preoperative 106+/-94, postoperative 678+/-343 pmol/L; controls preoperative 124+/-79, postoperative 171+/-93 pmol/L) in the Maze group on the first postoperative day (p < 0.001). Preoperative baseline plasma levels of ANP and pulmonary capillary wedge pressures (PCWP) were higher in the Maze group but this difference was abolished by pacing, and postoperatively, ANP levels changed in parallel to the PCWP in both groups. Diuretic requirements were significantly higher in the Maze group. CONCLUSIONS: Substantial increases in ADH and aldosterone were observed after the Maze procedure, indicating these hormones as important determinants in postoperative fluid retention. The role for ANP in this setting may be a less prominent than previously reported.

Adult↗
PubMed2001

Postoperative stroke in cardiac surgery is related to the location and extent of atherosclerotic disease in the ascending aorta.

OBJECTIVES: The aim of the study was to evaluate the risk from calcified atheromas in the ascending aorta, and the extent and topography of the disease in the development of stroke after cardiac surgery. BACKGROUND: Postoperative stroke constitutes a serious problem in cardiac surgery, and atherosclerosis of the ascending aorta is an important risk factor. METHODS: Before surgical manipulation epiaortic echocardiographic ultrasound was performed to evaluate the ascending aorta in 921 consecutive patients undergoing cardiac surgery. The presence of calcification, location of atheroma, extent of the disease and clinical variables including postoperative stroke were recorded prospectively. RESULTS: A total of 26.2% of the patients had atherosclerosis of the ascending aorta, and in 44.4% of them more than one of 12 possible segments was involved. Logistic regression showed that atherosclerotic disease in the ascending aorta was the most important predictive factor for postoperative stroke. The incidence of stroke was 1.8% in patients without atherosclerotic disease of the ascending aorta, and 8.7% in patients with the disease (p < 0.0001). Diabetes mellitus was also a predictive factor (p = 0.04). A new and unique finding of this study was that the middle-lateral segment is an independent predictive factor for postoperative stroke, with a relative risk of 26% (p = 0.04). CONCLUSIONS: Patients with atheromatosis in the ascending aorta had an 8.7% incidence of postoperative stroke, in spite of minor surgical modifications. The risk depended on the presence, location and extent of the disease. Randomized trials evaluating alternative surgical strategies in coronary surgery are urgently needed in high risk patients.

Aortic Diseases↗
PubMed2001

Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease--12-month follow-up: angiogenic gene therapy.

OBJECTIVE: To test the safety and bioactivity of phVEGF-A165 after intramyocardial injection during 12-month follow-up. DESIGN: Open-labelled study. SUBJECTS: Inclusion criteria were angina pectoris, Canadian Cardiovascular Society (CCS) class III-IV, unamenable to further revascularization, ejection fraction (EF) >30%, perfusion defects extending over >10% of the anterolateral left ventricle wall detectable with adenosine single photon emission computerized tomography (SPECT) and at least one patent vessel visible by coronary angiography. Seven of 39 patients referred for gene therapy were included. INTERVENTION: Via a mini-thoracotomy under general anaesthesia. phVEGF-A165 was injected directly into the myocardium at four sites in the anterolateral region of the left ventricle. RESULTS: Operative procedures were uneventful. Perioperative release of myocardial markers and electrocardiogram (ECG) changes were detected in two patients. There were no perioperative deaths but one patient died 7 months postoperatively because of myocardial infarction. Plasma vascular endothelial growth factor (VEGF)-A levels increased two to threefold peaking 6 days postoperatively (P < 0.004) and returning to baseline by day 30. A significant reduction in angina pectoris was reported. The CCS class improved from 3.3+/-0.2 to 1.9+/-0.3 (P < 0.01) and nitroglycerine intake decreased from 39+/-15 to 12+/-5 tablets week(-1) (P < 0.001) 2 months after gene transfer. Improvements remained after 12 months when nitroglycerine consumption approached zero. Improved myocardial function in the phVEGF-A165 injection region was documented in all patients (P < 0.016) by tissue velocity imaging (TVI). Reduced reversible ischaemia was detected by adenosine SPECT in four patients. Improved collateralization was detected in four patients with coronary angiography. CONCLUSION: Intramyocardial injection of phVEGF-A165 is safe and may lead to improved myocardial perfusion and function with longstanding symptomatic relief in end-stage angina pectoris. Based on these results this therapeutic potential is being tested in a double-blind placebo controlled multicentre trial.

Aged↗
PubMed2001

Graft surveillance: venous pressure, access flow, or the combination?

BACKGROUND: Increased venous pressure (VP) and decreased access flow (Qa) are predictors of dialysis access graft thrombosis. VP is easily obtainable. Qa assessment requires a special device and takes more time. The aims of our randomized multicenter studies were to compare outcome in patients with grafts monitored by VP or Qa (study A) or monitored by VP or the combination of VP and Qa (study B). METHODS: We performed VP measurements consisting of weekly VP at a pump flow of 200 mL/min (VP200) and the ratio of VP0/MAP. Qa was measured every eight weeks with the Transonic HD01 hemodialysis monitor. Threshold levels for referral for angiography were VP200> 150 mm Hg or VP0/MAP> 0.5 (both at 3 consecutive dialysis sessions) or Qa <600 mL/min. Subsequent therapy consisted of either percutaneous transluminal angioplasty (PTA) or surgery. RESULTS: Total follow-up was 80.5 patient-years for 125 grafts. The vast majority of a total of 131 positive tests was followed by angiography and corrective intervention. In study A, the rate of thromboses not preceded by a positive test was 0.19 and 0.24 per patient-year (P = NS), and in study B, it was 0.32 versus 0.28 per patient-year (P = NS). Survival curves were not significantly different between the subgroups. CONCLUSIONS: These data demonstrate that standardized monitoring of either VP or Qa or the combination of both and subsequent corrective intervention can reduce thrombosis rate in grafts to below the recommended quality of care standard (that is, 0.5 per patient-year, NKF-DOQI). These surveillance strategies are equally effective in reducing thrombosis rates.

Adult↗
PubMed2001

Myocardial Doppler tissue velocity improves following myocardial gene therapy with VEGF-A165 plasmid in patients with inoperable angina pectoris.

BACKGROUND: Myocardial tissue velocity and perfusion were studied in patients with severe angina pectoris following gene therapy by intramyocardial injection of phVEGF-A165 via thoracotomy. Plasma concentrations of VEGF-A increased postoperatively. Two months after treatment anginal status and myocardial tissue velocity improved and perfusion showed a tendency to improve. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy. OBJECTIVE: To study effects on myocardial tissue velocity and perfusion in patients with angina pectoris following intramyocardial injection of phVEGF-A165 via thoracotomy. DESIGN: Open label, phase I/II. METHODS: Six patients with Canadian Cardiovascular Society (CCS) angina pectoris functional class III - IV and with major defects at adenosine stress single-photon emission computerized tomography (SPECT) were studied. In addition to SPECT, coronary angiography and dobutamine stress echocardiography with tissue Doppler velocity imaging were performed before and two months after gene transfer. RESULTS: Plasma concentrations of VEGF-A increased 2 to 3 times (P < 0.04) over baseline from 2 to 14 days after injection with normalization after 4 weeks. The CCS class improved about 40%, from 3.3 +/- 0.2 to 2.0 +/- 0.3 (P < 0.02) and nitroglycerine consumption decreased 30 - 40%, from 44 +/- 17 to 15 +/- 5 tablets per week (P < 0.05). The maximal systolic myocardial tissue velocity increased in all patients about 25% (P < 0.02) but did not reach the reference range. Myocardial perfusion at SPECT improved in four of the six patients. CONCLUSIONS: Anginal status, myocardial tissue velocity and perfusion can be improved by phVEGF-A165 intramyocardial injection. Tissue velocity imaging appears to be a sensitive, objective method for detecting changes in myocardial function following gene therapy.

Aged↗
PubMed2000

Gustatory sweating and diabetes.

Gustatory sweating as a feature of autonomic neuropathy is an unusual phenomenon in diabetes mellitus. We describe a patient with type 1 diabetes mellitus complicated by retinopathy, nephropathy and neuropathy. This patient presented with bilateral diffuse facial sweating during eating. She was treated with the antimuscarine agent oxybutynine, which provided a striking relief from the gustatory sweating.

Adult↗
PubMed2000

The Maze operation for treatment of atrial fibrillation. Early clinical experience in a Scandinavian institution.

The Maze operation is a potentially curative surgical option in patients with disabling atrial fibrillation (AF) refractory to conventional treatment. The aim of this study was to evaluate the initial 4-year Maze experience in our institution. The study included 26 patients (19 males, mean age 55 years) who had undergone the Maze (III) operation between 1994 and 1998. Nine patients had surgery for concomitant heart disease. Follow-up was 3-55 (median 18) months. No deaths or neurological complications occurred; 22 patients are at present in regular sinus-, or junctional rhythm, 2 patients have permanent atrial pacing for symptomatic sinus node dysfunction, and 2 patients have had persistent AF, post surgery. Sinus node dysfunctions were detected in five patients, though not requiring pacemakers. Out of the total 26 patients, 23 are free of anti-arrhythmic drugs. Echocardiographic signs of left atrial contraction were recorded in 50% of the patients. The Maze operation offers a safe alternative to conventional therapy, with attractive results justifying expansion in the use of this treatment for AF.

Adult↗
PubMed1999

Antitumor immune effector mechanisms recruited by phage display-derived fully human IgG1 and IgA1 monoclonal antibodies.

We have constructed a recombinant, fully human IgA1 monoclonal antibody, UBS-54/IgA1, against the tumor-associated Ep-CAM molecule and compared its tumor-killing capacity with its IgG1 counterpart in in vitro assays. The data show that phage display-derived fully human IgA1 antibodies efficiently recruit immune effector cells that express the Fc receptor for IgA, FcalphaRI (CD89). UBS-54/IgA1-mediated killing of tumor cells by isolated polymorphonuclear cells (PMNs) and in whole blood was found to proceed without the necessity to preactivate effector cells with cytokines. In addition, the IgA1 anti-Ep-CAM human monoclonal antibody (huMab) triggered phagocytosis of tumor cells by monocyte-derived macrophages. Strikingly, simultaneous addition of IgA1 and IgG1 anti-Ep-CAM antibodies did not result in enhancement of tumor cell killing unless the effector cells were stimulated with granulocyte colony-stimulating factor. The lack of an additive effect could be attributed to an inhibitory effect of IgG on IgA-mediated tumor cell killing through binding of IgG1 to the inhibitory FcgammaRIIb receptor expressed by PMNs. These results show that IgA1 antitumor huMabs are capable of recruiting the large population of peripheral blood PMNs for tumor cell killing. This population is not effectively recruited by IgG type antibodies, currently the antibodies most frequently used for clinical application. In addition, the data suggest that a combination of IgG1 and IgA1 antitumor huMabs may collaborate in tumor cell killing in patients treated with granulocyte colony-stimulating factor.

Antibodies, Monoclonal↗
PubMed1999

Elimination of cholesterol as cholestenoic acid in human lung by sterol 27-hydroxylase: evidence that most of this steroid in the circulation is of pulmonary origin.

Human alveolar macrophages have exceptionally high capacity to convert cholesterol into 27-hydroxycholesterol and cholestenoic acid by the sterol 27-hydroxylase mechanism. It is shown here that the human lung has a higher content of 27-hydroxycholesterol relative to cholesterol than any other organ. In order to evaluate the importance of the sterol 27-hydroxylase mechanism for cholesterol homeostasis in the lung, the production of cholestenoic acid by human lung was investigated. Removal of one lung reduced the level of cholestenoic acid in the circulation by 48 +/- 4% (P < 0.005). The levels of cholestenoic acid in the pulmonary artery and in the pulmonary vein showed significant differences (P < 0.002) with higher levels in the pulmonary vein (108 +/- 16 and 104 +/- 16 ng/mL, respectively). This corresponds to a net flux of cholestenoic acid from the lung of about 14 mg/day, which is more than 80% of the reported removal of this oxysterol and its metabolites from the circulation by the liver per day. Bypassing the lung for 60 min led to a reduction in circulating cholestenoic acid (30%) that fits with a pulmonary origin when taking into account the half-life of cholestenoic acid. The level of circulating cholestenoic acid was found to be less in patients with different lung diseases. It is evident that most of the cholestenoic acid in the circulation is of pulmonary origin. The present results suggest that the sterol 27-hydroxylase in the lung is responsible for at least half of the total flux of 27-oxygenated cholesterol metabolites to the liver and that this enzyme system may be of importance for cholesterol homeostasis in the lung.

Cardiopulmonary Bypass↗