PubMed Health⌕ Search

Biomedical subjects

B Höfling

Publications and source records attributed to B Höfling.

At least 91 records · Page 5Linked to original sources

[Uptake and distribution of hematoporphyrin derivatives (HPD) in arteriosclerotic and normal vessel segments].

Percutaneous treatment of vascular disease is limited by a relatively high long-term restenosis rate. Proliferation of smooth muscle cells may be one of the major reasons for restenosis. Therefore, due to its selective cytotoxic effect, photodynamic therapy (PDT) with HPD-injection and local laser light-application might be a promising therapeutic principle as prophylaxis of restenosis. Up to now, PDT has been used clinically in the treatment of superficial tumors. We studied its potential application as an antiproliferative modality for restenosis prophylaxis. Basic conditions for therapeutic use are: uptake of HPD in arteriosclerotic vessels; arteriosclerotic lesions show a higher photosensitivity than normal vessel after application of HPD. We investigated the uptake of HPD (Photofrin II) in normal (n = 15) and arteriosclerotic (primary lesions n = 52; restenosis n = 10) human vessel segments using quantitative fluorescence detection after incubation with 2.5 micrograms and 5 micrograms HPD/ml cell culture medium. HPD content, as reflected by fluorescence intensity, was measured after 15, 30, 60 min, and 24 h of incubation. Fluorescence intensity was concentration-dependent, with 80% of the maximal uptake reached at 1 h. A preferential uptake of HPD was measured in arteriosclerotic as compared to normal vessel segments (primary lesion: fluorescence-ratio of 3:1 at 1 h; restenosed lesion: fluorescence-ratio of 4:1 at 1 h). In addition, highly cellular plaque segments like restenosed material showed markedly increased fluorescence as compared to acellular matrix. Uptake of HPD was quickly (within 1 h) and preferentially detected in arteriosclerotic segments. A selective cytotoxic effect when combined with laser light may result and could be applied to restenosis prophylaxis.

Arteriosclerosis↗

[Selective hematoporphyrin derivative (HMD) application in arterial vessels using a porous balloon catheter results in equivalent levels as compared to high-dose systemic administration].

The treatment of atherosclerotic vascular stenosis with percutaneous angioplasty is limited by a rate of restenosis of about 20-40%, in spite of new angioplasty devices. Histological and immune histological examinations of restenosed material obtained by coronary atherectomy indicate that cellular proliferation is an important determinant of restenosis. With the use of photodynamic therapy (PDT), it might be possible to selectively impair proliferating tissue by the application of the photosensitizer Photofrin II (a hematoporphyrin-derivative, HPD) followed by localized laser-light radiation. With the knowledge of the success of PDT in tumor therapy, the extension of the application of PDT in prophylaxis of restenosis should be examined. The technique used up to now works with the systemic application of the sensitizer. By applying HPD locally, however, one might be able to reduce the amount of the photosensitizer, but still achieve an equally cytotoxic effect. A recently developed catheter with a porous balloon enables local application of HPD. The following study describes the uptake and distribution of the hematoporphyrin-derivative Photofrin II within the walls of elastic and muscular type vessels after systemic and selective application. In 20 rabbits and seven pigs, Photofrin II was applied systemically (5 mg/kg i.v.) and locally (5 ml of 2.5 mg/ml). From each animal 12 vascular specimens (six arterial segments of either muscular and elastic type) were removed at a definite time within a defined period of 5 min to 24 h after application. To quantify the uptake of Photofrin II, we used fluorescence microscopy with digital image processing. After systemic application there was an increase of Photofrin II over a 4-h period. In contrast, a maximum concentration of Photofrin II was measured immediately after local application and found to be decreasing over a period of 4 h. The intima showed the highest uptake of HPD, both after local and systemic applications, as compared to uptake by the media and adventitia. The intimal uptake was significantly higher after local than after systemic application. Media and the adventitia showed, respectively, only one-half and one-fifth of the intima's intake. The rapid increase of the HPD concentration after local application would make PDT feasible in restenosis prophylaxis immediately after angioplasty without systemic side-effects of the photosensitizer.

Administration, Topical↗

[Directional coronary atherectomy: acute results and angiography follow-up in 42 treated patients].

We used directional coronary atherectomy (DCA) as a therapeutic option for coronary lesions unsuitable for PTCA (eccentric, ostial, branching or restenotic) and as "rescue device" for failed PTCA. Forty-two patients were treated by DCA using the Simpson coronary atherectomy device, including four female and 38 male patients with an average age of 55.7 years. Atherectomy as primary intervention was performed in 16 patients (Group I), because morphology of their lesions was assumed to be unsuitable for PTCA. DCA was also used after failed balloon dilatation in eight patients with unsuccessful, but uneventful treatment (Group II). In 18 cases (Group III) DCA was performed as "rescue procedure" after failed PTCA and resulting critical ischemia (local dissection, signs and symptoms of ongoing ischemia, occlusion after PTCA). Target lesions were located in LM 1, LAD 33, RCA 9, CABG 3. Mean length of lesion was 8.1 mm (2-25 mm). The overall success rate for 46 lesions was 93%. Mean stenosis was reduced from 92% to 17% in cases with primary success. Presently, available follow-up angiography (24) showed six restenoses (defined as greater than 50% stenoses). Major complications occurred in seven cases (death: 0, MI: 2, CABG within 24 h: 5; 3 in Group III). "Rescue indication" (Group III) after failed balloon dilatation procedure showed a favorable primary result with a success rate of 78%; only three cases of this group needed CABG. Our results show that DCA is a safe and effective technique which can extend the indication for percutaneous procedures and gives a successful nonoperative option in cases of failed PTCA.

Angioplasty, Balloon, Coronary↗

[Increased in vitro motility of human vascular wall myocytes from restenotic lesions of peripheral and coronary vessels].

In this study we report on the successful cultivation of human peripheral and coronary plaque specimens selectively retrieved by percutaneous Simpson atherectomy and obtained by direct operative approach. A total of 32 patients in whom plaque tissue was excised from 22 primary and 10 restenotic lesions comprise the study population. Irrespective of their origin or location, all advanced lesions showed smooth muscle cells (SMC) to be their predominant cell type proven by indirect immunofluorescence technique. Cultured endothelial cells were only identified in 2/6 surgically removed samples. Locomotion analysis of cultured smooth muscle cells was performed with a standardized computer-assisted video system. Cells of all groups exhibited random motility. However, SMC migratory velocity of restenotic origin amounted to 47.4 +/- 3.4 microns/h (n = 10, x +/- SD) and thereby was found 2.4 times (p less than 0.001) increased as compared to primary lesion values of 22.0 +/- 3.7 microns/h (n = 22, x +/- SD). This highly significant difference was seen for both peripheral and coronary lesions. Our data suggest increased SMC migratory activity to represent a basic biological mechanism involved in human accelerated arteriosclerosis and restenosis formation.

Aged↗

Percutaneous peripheral atherectomy: angiographic and clinical follow-up of 60 patients.

The Simpson atherectomy catheter was used to treat 60 patients with a total of 94 lesions comprising 63 stenoses (mean length 1.1 +/- 0.5 cm) and 31 occlusions (4.2 +/- 2.9 cm) of the superficial femoral (n = 77), popliteal (n = 8), iliac (n = 8) and anterior tibial (n = 1) arteries. The immediate angiographic success rate was 90% for both occlusions and stenoses, and clinical success was obtained in 82% of patients. The stenoses were reduced from 83 +/- 13% to 17 +/- 18% acutely and to 31 +/- 26% at 6 months; the occlusions were reduced from 100% to 9 +/- 9% initially and to 60 +/- 34% at 6 months. Angiographic restenosis was found in 24% of lesions: 23% in concentric and 11% in eccentric lesions and 47% in total occlusions. At 1 year, 72% of patients had clinically patent arteries with maintained Doppler index and walking distance. Three of four patients undergoing repeat atherectomy had a second restenosis. In summary, the procedure was found to be safe and effective in the treatment of peripheral vascular disease. It appears to be particularly beneficial in the treatment of eccentric stenoses and is not limited by the presence of calcification.

Aged↗

Invasive strategy for treatment of myocardial infarction.

The classical approach to the treatment of acute myocardial infarction (MI) has been one of stabilization and complication management. In an effort to optimize treatment, the initiation of the cardiac care unit and the use of antiarrhythmic therapy have succeeded in lowering the mortality rate substantially. More modern concepts are aimed at limiting infarct size and preserving myocardial function. These aims can be achieved medically using intravenous (i.v.) thrombolysis or invasively either with intracoronary (i.c.) thrombolysis, percutaneous transluminal coronary angioplasty (PTCA), or bypass surgery. Although i.c. thrombolysis is more effective than the i.v. route, the necessity for acute coronary catheterization makes it incompatible and difficult for routine use, and thus is usually reserved for cases in which i.v. lysis has failed. Intravenous thrombolysis is becoming the standard approach to MI, and the remaining questions are those of which drug and dosage are optimal and how to approach the patient after thrombolysis. In this regard, we favor a symptom-guided approach, as shown by the TIMI-IIA and European cooperative studies. In patients with ongoing ischemia postlysis, heart catheterization is indicated and a decision regarding PTCA or surgery is then made, depending on anatomy. In patients remaining stable after acute lysis, a predischarge stress may help in selecting patients requiring catheterization. As an alternative invasive approach to acute MI, PTCA may be the quickest and most effective method to recanalize a vessel, but, again, logistical problems make it incompatible in the acute setting. The same is true for bypass surgery, and although extensive improvements have been made in intraoperative myocardial preservation so that a 2% mortality is achievable, it is reserved for patients with extensive ischemia and anatomy unsuitable for PTCA (extensive multivessel or left main disease).

Adrenergic beta-Antagonists↗

Circadian pattern of blood pressure and heart rate in the longer term after heart transplantation.

A loss of the circadian rhythm pattern of the blood pressure (BP) and heart rate (HR) as well as the development of hypertension has been found after heart transplantation (Htx). To determine whether a reappearance of this rhythm occurs in the long term after Htx, we used 24-h ambulatory monitoring to study 27 patients 1.7+/-1.6 years (range of 10 days to 4.3 years) after Htx. Patients were divided into two groups: group I (short term), Htx less than 6 months (n = 7); and group 2 (long term), Htx more than 6 months previously (n = 20). Group 2 had significantly higher diastolic BP as well as a greater fall in systolic BP during the night (-0.4+/-8.0 vs. 9.0+/-7.2 mm Hg, p < 0.01). There was also a higher day HR found in group 2 (73.2+/-14.5 vs. 96.8+/-12.5 beats/min, p < 0.001) as well as a larger fall in night HR in group 2 (4.2+/-5.5 vs. 11.9+/-4.9 beats/min, p < 0.005). The return of the circadian rhythm pattern in the longer term after Htx may result from partial reinervation of the heart, although other neurohumoral factors or concomitant medication (lower steroid dosages) may play a role.

Adult↗

[Possibilities of arterioscopy].

Today, technically optimized fiberoptical systems have become available for direct visualization of the arterial inner wall. The increasing significance of interventional revascularization techniques opens the door to new adjuvant diagnostic and therapeutic indications for arterioscopy, in addition to the earlier mainly intraoperative use. Especially for vascular wall reconstruction with percutaneous atherectomy, the angioscopic identification of residual intraluminal plaque material helps to optimize the procedure. On the basis of our own experience, a critical evaluation of arterioscopy is presented.

Arterial Occlusive Diseases↗

Cell constitution and characteristics of human atherosclerotic plaques selectively removed by percutaneous atherectomy.

The Simpson atherectomy device used for the recanalization of severely stenosed peripheral arteries is able to collect plaque material which can be further characterized. This study reports histological, immunohistochemical and transmission electron microscopic findings on advanced human primary atherosclerotic plaques of peripheral arteries percutaneously removed by a Simpson atherectomy catheter. Material from stenosing plaques consisted of dense connective tissue with abundant amounts of concentrically arranged elastic fibers and lamellae. This meshwork contained numerous cells, often arranged in clusters and oriented with their longer axis parallel to the direction of blood flow. The vast majority of these cells could be easily identified as vimentin-positive and desmin-negative smooth muscle cells containing lipid deposits in the perinuclear region and numerous glycogen particles. Monocytes/macrophages were observed only very infrequently. Plaque tissue contained a range of smooth muscle cell phenotypes. Most of the cells were of an intermediate phenotype, i.e. sparsely filled with myofilament bundles at the cell periphery and a high amount of organelles such as mitochondria, rough endoplasmic reticulum and Golgi cisterns. An intact lining of pieces of intimal tissue with endothelial cells was not observed. Two-dimensional gel electrophoresis of plaque tissue showed the presence of alpha-, beta- and gamma-actin isoforms with a clear predominance of the beta-isoform.

Arteriosclerosis↗

Multiple lead monitoring during and after PTCA.

We investigated whether optimized ischaemia monitoring during and after PTCA using continuous recording of standardized 12-lead ECG provides additional information regarding the presence and localization of ischaemia. We studied 50 patients undergoing PTCA who received a total of 173 balloon inflations. Chest leads showed not only significantly more frequent ischaemic changes compared with routine limb lead monitoring (116/173 (67%) vs 88/173 (51%)), but in addition, a significantly earlier appearance of changes; 15.4 +/- 6.2 s after the start of balloon inflation compared with 17.5 +/- 6.8 s in the limb leads. Anginal pain, however, first occurred at 35 +/- 14 s after vessel occlusion in 74/173 (43%) of inflations. The changes in ECG monitoring correlated well with the coronary wedge pressure; at coronary wedge pressures below 20 mmHg, 97% of inflations caused ischaemic ECG changes; at pressures greater than 40 mmHg, changes were noted in only 42% of inflations. PostPTCA, 6/36 (16.7%) patients undergoing continuous 12-lead monitoring showed ischaemic ST-segment changes (asymptomatic in five cases), which helped in decision-making regarding interventional measures. In summary, we have found standardized 12-lead monitoring both during and after PTCA to be more precise and reliable in ischaemia detection and useful for clinical decision making.

Angioplasty, Balloon, Coronary↗

[Angiography and functional results and histologic findings following percutaneous atherectomy in patients with arterial occlusive disease].

In this study we report on the atherectomy technique, acute and long-term data, and histological findings of excised specimens from patients with peripheral vascular disease treated with the Simpson atherectomy catheter. Forty patients with a total of 72 lesions of the iliac (n = 5), superficial femoral (n = 62), and popliteal (n = 5) arteries could be treated; five patients had rest pain and two had gangrene. The primary success rate (of all lesions, including total occlusions and longer stenoses) was over 90%. The percent of stenosis decreased from 87.2 +/- 19.9% to 16.6 +/- 15.5%; the claudication distance improved from 80.5 +/- 65.7 m to 152.8 +/- 80.3 m; the Doppler index (leg/arm) increased from 0.57 +/- 0.17 to 0.81 +/- 0.16. At 6 months the mean walking distance and Doppler index remained stable from post-atherectomy; the mean percent of stenosis had increased to 35.7 +/- 30.9%. The angiographic restenosis rate (defined as stenosis greater than 70%) was 21% with a clear difference found depending on the primary morphology of the lesion: in eccentrics 5%, concentrics 27%, and total occlusions 42%, thereby allowing categorization of the suitability of a primary lesion for atherectomy. Histologically, restenoses showed more cellular proliferation and organized thrombus as compared to their primary stenoses; further investigations (cell culture, immunohistochemistry, and electron microscopy) are underway.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗