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Biomedical subjects

Rainer Schmid

Publications and source records attributed to Rainer Schmid.

At least 19 recordsLinked to original sources

Multiple substance use among young males.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Adolescent↗

Randomized comparison between intracoronary beta-radiation brachytherapy and implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent restenosis.

BACKGROUND AND PURPOSE: Intracoronary brachytherapy was the primary therapeutic option for the treatment of in-stent restenosis (ISR) during the last years. Especially for the treatment of diffuse ISR (lesions >10mm), beta-source brachytherapy was significantly superior to singular balloon angioplasty. Despite lacking clinical database, the implantation of drug eluting stents recently became a common procedure for the treatment of ISR. This randomized trial aimed to compare the efficacy of beta-brachytherapy with beta-radioisotopes (90)Sr/(90)Y and paclitaxel-eluting stent implantation for the treatment of diffuse ISR. MATERIAL AND METHODS: Thirty-seven patients with diffuse ISR were randomly assigned to beta-brachytherapy after balloon angioplasty (Beta-Cath in 17 patients) or paclitaxel-eluting stent implantation (Taxus-Express2 in 20 patients). Six-month clinical follow-up was obtained for all patients, while angiographic follow-up was available for 30 patients. RESULTS: Binary ISR (restenosis >50%) within target segment was observed in three patients treated with Beta-Cath, of which one needed target segment revascularisation for recurrent ISR, whereas no significant restenosis occurred in the patients treated with Taxus-Express2 (P=0.037). No further major adverse cardiac (target segment revascularisation, myocardial infarction, death) was found in either group (P=NS). Stent implantation was the more time-saving (31+/-11 min versus 60+/-23 min, P<0.001) procedure. CONCLUSIONS: Although this trial revealed a significant reduction of binary restenosis in the Taxus-Express2 arm, we found no difference in clinical outcome after implantation of paclitaxel-eluting stents for the treatment of diffuse ISR when compared to beta-brachytherapy.

Angioplasty, Balloon, Coronary↗

Single-dose pharmacokinetics of cefodizime in critically ill elderly patients.

Cefodizime is an extended-spectrum third-generation cephalosporin antibiotic that is widely used in the treatment of severe infections of the respiratory and urinary tracts. Pharmacokinetic characteristics of cefodizime were assessed in 13 critically ill elderly patients (median age 73+/-6 years). The mean cefodizime peak serum concentration following a single 2g cefodizime infusion was 219+/-58 mg/L and the mean trough level 12 h after infusion was 29+/-17 mg/L. The elimination half-life was 6.19+/-2.45 h. Total body clearance, area under the plasma concentration-time curve and volume of distribution were 35.8+/-13.2 mL/min, 1089.4+/-505.3 mg h/L and 17.4+/-6.3 L, respectively. Pharmacokinetics of cefodizime in critically ill elderly patients were comparable with those reported previously in healthy volunteers.

Aged↗

Epidemiology of substance use in a representative sample of 18-year-old males.

AIMS: To assess recent drug use through urine testing as well as the prevalence of tobacco and alcohol dependence among young males and to analyse the associations between tobacco dependence and cannabis use (delta-9-tetrahydrocannabinol, THC), tobacco dependence, and alcohol dependence as well as between THC use and other illicit drug use. METHODS: Urine samples were collected, and nicotine and alcohol questionnaires were administered. Carbon monoxide was assessed in exhaled air. Data from young males from representative, selected districts of Lower Austria were recorded during the annual physical examination for mandatory military service. Out of all 18-year-old males in Austria 3.8% (n = 1902) were included in the study. Prevalence of recent illicit drug use, tobacco dependence (heavy smoking index, HSI), alcohol dependence (The 4-item cutting down, annoyance by criticism, guilty feeling, and eye-openers (CAGE) questionnaire), and associations between substance categories by means of logistic regression analyses were calculated. RESULTS: Alcohol abuse was found in 15.1% and alcohol dependence was found in 3.2%. According to the HSI 51.5% of males reported daily smoking, of whom 43.7% showed a mild level, and 7.8% a high level, of nicotine dependence. About 5.1% of the sample evidenced THC in urine. Opiates were identified in 2.7% of urine samples. Smokers showed a higher risk of THC use. THC users had a tendency to use cocaine and amphetamines more frequently than THC abstainers. CONCLUSION: Nicotine and alcohol dependence is common among young males. Biological assessment of illicit drug use seems to confirm previous questionnaire-based findings of associations between THC use and other illicit drugs. Urine testing seems to be an adequate method to analyse associations of THC use and other illicit drugs. In combination with questionnaires urine testing may be used for the assessment of associations of tobacco dependence and recent illicit drug use based on epidemiological surveys.

Adolescent↗

Randomized blinded clinical trial of intracoronary brachytherapy with 90Sr/Y beta-radiation for the prevention of restenosis after stent implantation in native coronary arteries in diabetic patients.

BACKGROUND: We report a double-blind, randomized clinical trial of intracoronary beta-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients. METHODS: After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with beta-radiation with 18 Gy at 1 mm vessel depth (n = 53) or placebo treatment (n = 53). RESULTS: Angiographic analysis at 9 month follow-up revealed a late lumen loss of 0.7+/-0.9 mm in the radiotherapy group versus 1.2+/-0.8 mm in the control group at the injured segment (P = 0.006), 0.9+/-1.0 versus 1.3+/-0.7 mm at the radiated segment (P = 0.02), and 0.9+/-1.0 versus 1.3+/-0.7 mm at the target segment (P = 0.04) (defined as active source length plus 5mm on proximal and distal sites). Binary restenosis rates were significantly lower in the radiation group in all subsegments (injured segment: 10.9 versus 37.3%, P = 0.003; radiated segment: 21.7 versus 49.0%, P = 0.005; target segment: 23.9 versus 49.0%, P = 0.01). Target lesion revascularization for restenosis was required in nine lesions (17.6%) in the radiotherapy group versus 18 (34.0%) in the placebo group (P = 0.05). Late thrombosis occurred in four radiated patients (after premature discontinuation of antiplatelet therapy in all), resulting in a major adverse clinical event rate of 37.2% in the brachytherapy group versus 38.6% in the placebo group (P = ns). CONCLUSIONS: In diabetic patients with de novo coronary lesions, intracoronary radiation after stent implantation significantly reduced restenosis. However, this clinical benefit was reduced by the frequent occurrence of late thrombosis.

Aged↗

Coffee consumption induces GSTP in plasma and protects lymphocytes against (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced DNA-damage: results of controlled human intervention trials.

A number of animal studies indicate that coffee protects against chemical induction of cancer; also human studies suggest that coffee consumption is inversely related with the incidence of different forms of cancer. The protective effects were attributed to induction of glutathione-S-transferases (GSTs) and aim of the present human study was to find out if coffee causes induction of GSTs and protects against DNA-damage caused by (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), the DNA-reactive metabolite of benzo(a)pyrene. Ten participants consumed 1L unfiltered coffee/d over 5 days. Before and after the intervention, saliva and blood were collected and the overall GST activity was measured with 1-chloro-2,4-dinitrobenzene (CDNB). Additionally, GSTP and GSTA were determined in plasma with immunoassays. In blood, only weak (p=0.042) induction of GST (CDNB) was found. Furthermore, pronounced (three-fold) induction of GSTP was observed in blood, whereas GSTA was not altered. No correlations were seen between induction of GST (CDNB) and GSTP activities and the GSTP1 genotypes of the participants. Also clinical parameters (creatinine, alanine, aminotransferase, aspartate aminotransferase, alkaline phosphatase), which are markers for organ damage, were monitored. None of them was altered by coffee, but serum cholesterol levels were slightly (not significantly) enhanced. In a second trial (n=7), GSTP induction by unfiltered and paper filtered coffees, differing in cafestol and kahweol contents, were compared. The participants consumed 1L coffee/d over 3 days. Again significant (three-fold) induction of GSTP was observed. The effects seen with the two coffees were identical, indicating that the diterpenoid concentrations are not responsible for the effects. In a further trial (n=7), the effect of coffee (unfiltered, 1L/d, 5 days) on BPDE induced DNA-migration was studied in comet assays. A 45% reduction effect was observed. Our findings show that coffee induces GSTP in humans and indicate that consumption may lead to protection towards polycyclic aromatic hydrocarbons.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

3D-conformal radiotherapy for prevention of carotid recurrent in-stent restenosis. Initial experience.

OBJECTIVE: To investigate 3D-conformal external beam radiotherapy for prevention of recurrent instent restenosis after carotid artery angioplasty. PATIENTS AND METHODS: Between Oct 2000 and Sep 2001 five patients with recurrent carotid artery in-stent restenosis of more than 50% lumen loss diagnosed with duplex sonography were enrolled. After successful revascularization, radiotherapy treatment planning was performed, which was based on the angioplasty protocol and all images documenting the intervention. A single dose of 5 Gy was prescribed to the 100% isodose. The treatment started on day one after angioplasty. In total, 4 fractions were given within 3 days. RESULTS: All patients tolerated the treatment well. No acute radiotherapy associated side effects were observed. Two patients developed recurrence within four months after therapy. In both cases, late total occlusion of the stent was noticed. One patient died and one developed a severe stroke. The other three patients remained asymptomatic with evidence of less than 50% restenosis. CONCLUSION: 3D-conformal radiotherapy is a feasible treatment option for highly selected patients with carotid artery in-stent restenosis. These preliminary results from a very small group of patients do show some potential for radiotherapy to prevent restenosis. However, due to the risk of late stent thrombosis, radiotherapy for the prevention of recurrent carotid artery in-stent restenosis is not recommended.

Aged↗

Alpha-tocopherol in plasma, red blood cells and lenses with and without cataract.

PURPOSE: To compare levels of alpha-tocopherol in human lenses with cataract to clear human lenses and to determine associations between levels of alpha-tocopherol in plasma, red blood cells, and human lenses with cataract. DESIGN: Cross-sectional study. METHODS: Concentrations of alpha-tocopherol were measured by high-performance liquid chromatography in blood and in human lenses with and without cataract. Lenses were obtained during cataract surgery and from a regional eye bank. Peripheral alpha-tocopherol status in patients was assessed as plasma alpha-tocopherol (total and corrected for low-density lipoproteins) and as red blood cell bound alpha-tocopherol. Data (mean +/- standard error of the mean) are expressed as microM alpha-tocopherol/g lens protein, microM alpha-tocopherol/l plasma, microM alpha-tocopherol/g low-density lipoproteins, and microM alpha-tocopherol/T red blood cells. RESULTS: Concentrations of alpha-tocopherol were measured in 27 lenses of cataract patients, 8 cadaver lenses with cataract and in 14 clear cadaver lenses. The concentration of alpha-tocopherol was significantly higher in cataract than in control cadaver lenses (0.49 +/- 0.04 vs 0.35 +/- 0.03, P < .05). The difference between alpha-tocopherol in lenses of cataract patients and control cadaver lenses was even higher (0.7 +/- 0.1 vs 0.35 +/- 0.03, P < .01). No significant correlation was observed between plasma alpha-tocopherol or red blood cell bound alpha-tocopherol and lens alpha-tocopherol in patients. CONCLUSIONS: Serum and red blood cell levels of alpha-tocopherol may not reflect the alpha-tocopherol status of the lens itself and therefore may not be clinically relevant markers for cataract risk. Mechanisms leading to increased levels of alpha-tocopherol in cataract lenses need to be explored in future research.

Aged↗

Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study.

BACKGROUND AND PURPOSE: The aim of the trial was to investigate the effect of Iridium-192 gamma endovascular brachytherapy on reduction of restenosis after femoropopliteal angioplasty. PATIENTS AND METHODS: Between Oct, 1998 and Jul, 2001 a total of 134 patients have been randomized after successful angioplasty to brachytherapy or sham irradiation in a prospective, randomized, multicenter, double blind controlled trial. Patients with de novo lesion of at least 5 cm or recurrent lesion of any length after prior angioplasty have been enrolled. Brachytherapy was performed with 7F centering catheter. Mean lesion length was 9.1cm (1.5-25 cm) and mean intervention length 13.6 cm (4-27.5 cm) in brachytherapy cohort. RESULTS: In placebo cohort mean lesion length was 10.3 cm (2-25 cm) and mean intervention length 14.1 cm (2-29 cm). A dose of 18 Gy was prescribed 2 mm from the surface of centering balloons. Analyzed (based on angiography) on intention to treat basis the binary restenosis rate at 12 months was 41.7% (28/67) in brachytherapy cohort and 67.1% (45/67) in placebo cohort (chi2 test, P<0.05). Corresponding data for as treated analysis (A total of 38 patients was excluded from analysis due to lack of follow-up, early recurrence within 30 days and >30% residual stenosis after angioplasty) have been 23.4% in the brachytherapy and 53.3% in the placebo group (P<0.05), respectively. The cumulative patency rates after 24 months on intention to treat analysis were 54% in the brachytherapy and 27% in the placebo group (P<0.005). Corresponding data for as treated analysis were 77% in the brachytherapy and 39% in the placebo group (P<0.001). Late thrombosis was not seen. CONCLUSIONS: Significant reduction of restenosis rate was obtained with endovascular gamma brachytherapy after femoropopliteal angioplasty.

Aged↗

Transfusion-related exposure to the plasticizer di(2-ethylhexyl)phthalate in patients receiving plateletpheresis concentrates.

BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that can leach from medical devices including storage bags for plateletpheresis concentrates (PCs). In this study, the DEHP exposure to patients receiving PCs was determined and several variables were evaluated to reduce DEHP load to PC recipients. STUDY DESIGN AND METHODS: In 12 patients, serum DEHP was assessed before and after PC transfusion. For in vitro investigations, PCs were produced either with donor plasma or with 65 percent additive solution (AS; T-Sol) and stored for 5 days. Washing of PCs was performed according to AABB standards. DEHP levels were determined by gas chromatography-mass spectrometry. RESULTS: Transfusion of PCs led to a significant increase in serum DEHP. DEHP levels in the PCs continuously increased during storage, although the accumulation of DEHP was less in PCs stored in the AS, T-Sol, than when stored in plasma. Storage-related accumulation of DEHP contributed to a major part of the total DEHP load in PCs stored for 5 days. Washing of PCs led to a reduction of DEHP load. CONCLUSION: Recipients of PCs are exposed to DEHP, although the total amount represents only a small percentage of the defined tolerable intake. Reduction of storage time, the storage of PC in T-Sol, or the exchange of the storage medium before transfusion are practicable means to reduce the DEHP load in PC.

Adult↗

Quality assurance in intracoronary brachytherapy. Recommendations for determining the planning target length to avoid geographic miss.

BACKGROUND AND PURPOSE: A new method of assessing geographic miss (GM) in endovascular brachytherapy (EVBT) is applied to evaluate the quality of intracoronary brachytherapy treatments, retrospectively. Based on the Vienna experience, recommendations for adequate safety margins are derived to avoid GM. PATIENTS AND METHODS: Evaluation is done on 136 vessels of 128 consecutive patients treated between October 1999 and July 2001. The quality of EVBT is assessed using the concept and terminology of the EVA GEC ESTRO task group. Evaluation of GM and/or safety margin is performed by comparing the outermost interventions with the reference isodose length (RIL) of the applied delivering devices on recorded compact disk (CD) angiograms. The RIL is defined as the length of the vessel segment, which receives at least 90% of the reference dose at the reference depth (=1 mm within the vessel). GM is defined as injured vessel segments, which receive a dose lower than 90% of reference dose. Measurements of intervention length (IL) and active source length (ASL) are performed with respect to anatomical landmarks within the vessel in the region of interest (e.g. stent edges), and by using the nominal length of the devices (balloons, sources) as a reference scale. The edges of RIL are determined by subtracting the length of the dose-fall-off zone (specific to the applied delivery devices: (192)Ir 4.5 mm, (90)Sr 2.5 mm, (32)P 2.0 mm) from the edges of ASL. RESULTS: The described method to assess GM is applicable to 128 vessels (94%). GM is found in 23% of proximal edges and 20% of distal edges. 95% of all GM are observed if the total margin (proximal+distal margin) between RIL and IL is shorter than 10.5 mm. CONCLUSIONS: GM in intracoronary brachytherapy can be widely avoided by adding an appropriate safety margin to the IL (5-6 mm each edge in this study) in order to determine the necessary RIL for a treatment.

Brachytherapy↗

Basic treatment planning parameters for a 90Sr / 90Y source train used in endovascular brachytherapy.

Working groups of the AAPM, DGMP, and ESTRO have published recommendations for endovascular brachytherapy, introducing concepts of relevant parameters for dose specification and treatment planning. However, the procedures for this treatment remain often mainly based on trial protocols and manufacturer instructions. Treatment planning requires the essential knowledge of the radial and longitudinal dose distribution, as well as information about geometrical uncertainties. The present study includes a whole data set for daily clinical practice using a commercially available device for endovascular brachytherapy (Novoste Betacath). The dose distribution around the 90Sr seed train was calculated with Monte-Carlo algorithms and verified by film dosimetry. The radial dose profile was determined starting from the surface of the delivery catheter Calculated dose profiles were in good agreement to measured values. The geometrical uncertainties were estimated with a retrospective analysis of 51 patient treatments. This shows the importance of using a safety margin of at least 10 mm between Intervention Length and Reference Isodose Length. Based on the longitudinal dose profile and the necessary safety margins, the maximum treatable intervention length is 25 mm and 45 mm for a 40 mm and 60 mm source train, respectively.

Algorithms↗

Intracoronary brachytherapy with beta-radiation for the treatment of long diffuse in-stent restenosis.

OBJECTIVE: To assess the efficacy of intracoronary brachytherapy with beta-radiation (Sr/Y) for the treatment of long diffuse in-stent restenosis (ISR). METHODS: As recurrent ISR depends on intimal injury after coronary angioplasty, long in-stent restenotic lesions were defined as lesions with a treatment length >26 mm (lesion length >20 mm plus a treatment margin of 3 mm at each end). Seventy-eight patients with long ISR were treated at our institution with beta-brachytherapy after coronary angioplasty. Patients were irradiated with either an approximate dose of 12 Gy at 1 mm vessel wall depth or with 18 Gy at 1 mm vessel wall depth. Clinical follow-up was available for 69 patients and angiographic follow-up for 65 patients. Late lumen loss (LLL), binary restenosis (stenosis >50%), target lesion revascularization (TLR) and major adverse cardiac events (MACE) were assessed for a follow-up time of 6.6+/-2.2 months. RESULTS: Mean interventional treatment length was 46+/-18 mm. TLR was performed in all 23 patients with binary restenosis (33%). Death of cardiac cause was reported for two patients, one of whom did not undergo TLR. Thus, overall MACE rate was 35%. Recurrent ISR was significantly more frequent in patients with geographic miss. Comparison of the different radiation dose regimens revealed significantly lower LLL in patients irradiated with the higher dose (0.20+/-0.68 mm compared with 0.65+/-0.96 mm, P=0.03). CONCLUSION: Intracoronary brachytherapy with beta-radiation (Sr/Y) is a safe and effective therapeutic option for the reduction of recurrent ISR in long diffuse lesions. We recommend a high-dose irradiation with 18 Gy at 1 mm vessel wall depth.

Aged↗

Increased dosage during intracoronary irradiation due to overlapped source stepping shows no long-term adverse changes in vessel morphology.

PURPOSE: The purpose of this analysis was to evaluate if overdosage during intracoronary irradiation due to overlapped source stepping may result in long-term morphologic changes in vessel anatomy. METHODS: Baseline angiograms of patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation with source stepping were analyzed. Overlapping was considered present for the segment with overlapped reference isodose length (RIL) (RIL = segment with > or = 90% of reference dose at 1 mm vessel wall depth). Baseline and 6-months follow-up volumetric intravascular ultrasound (IVUS) analysis were performed for the overlapped segment and for proximal and distal segments of equal length. RESULTS: Overlapping was found in six patients (three patients: (32)P treatment; three patients: (90)Sr/Y treatment); final analysis was performed in four patients. Comparison of the baseline and follow-up IVUS volumetric parameters revealed no significant change in lumen or vessel volumes at segments of overlaps in comparison to proximal and distal reference segments. CONCLUSION: Increased dosage due to overlapping during source stepping is not associated with morphologic changes in vessel anatomy at follow-up.

Angioplasty, Balloon↗

Blue- and green-light signals for gamete release in the brown alga, Silvetia compressa.

The intertidal brown alga Silvetia compressa releases gametes from receptacles (the reproductive tissue) rapidly upon a dark transfer (following a photosynthesis-dependent period in the light, termed potentiation). In this study, the wavelength-dependence of this process was investigated. During the potentiation period in white light (WL), gametes are not released. However, gametes were released during potentiation in blue light (BL), or in low red light/blue light (RL/BL) ratios, but not in RL alone, high RL/BL ratios, or in broadband blue-green light (B-GL) (presence of BL, but absence of RL). RL was as effective as WL for potentiation, i.e., both lead to gamete release following transfer to darkness. Rates of linear photosynthetic electron transport were similar in RL and BL. Gamete release in BL was inhibited by equal amounts of additional narrow-waveband light between the green and red regions of the spectrum, with light-induced gamete release restricted between <491 nm and 509 nm. Very little light-induced gamete release occurred between 530 nm and 650 nm. It is proposed that a BL-responsive photoreceptor is responsible for light-induced gamete release. Transfer of WL-potentiated receptacles to GL near 530 nm resulted in significant de-potentiation and reduced gamete release during a subsequent dark transfer. This effect was not seen at 509 nm or 560 nm and revealed the presence of a second photoreceptor system repressing or counteracting potentiation in the light. We propose that the restriction of gamete release to periods when irradiance is blue-shifted may constitute a depth-sensing mechanism for this intertidal alga, allowing controlled release of gametes at high tide and/or less turbid periods, thus minimizing gamete dilution, and promoting fertilization success.

Fertilization↗

Donor exposure to the plasticizer di(2-ethylhexyl)phthalate during plateletpheresis.

BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that is contained in most PVC devices, including apheresis disposables. Because DEHP can be extracted from apheresis disposables as the blood passes through the apheresis device, DEHP exposure was determined in healthy donors undergoing plateletpheresis performed with commercially available apheresis systems. STUDY DESIGN AND METHODS: The study population consisted of 36 healthy PLT donors undergoing plateletpheresis with either continuous or discontinuous apheresis devices. Serum concentrations of DEHP were determined from peripheral blood obtained before and after plateletpheresis, with gas chromatography-mass spectroscopy. RESULTS: Plateletpheresis performed with standard collection disposables resulted in a median increase of 232 percent of serum DEHP compared to levels before apheresis, corresponding to a total amount of DEHP exposed during a single apheresis of a median of 6.46 (range, 1.8-20.3) microg per kg of body weight. Endogenous levels of triglycerides showed a positive correlation with the amount of DEHP released. Increase in serum DEHP was short-term as serum DEHP rapidly returned to levels obtained before apheresis within 3 hours after completion of the apheresis course. Donor exposure to DEHP led to no variation in liver cell function within 48 hours after plateletpheresis. CONCLUSION: Commercial plateletpheresis disposables release considerable amounts of DEHP during the apheresis procedure, but the total dose of DEHP retained by the donor is within the normal range of DEHP exposure of the general population.

Blood Donors↗

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length.

OBJECTIVE: The goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BACKGROUND: Underdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. METHODS: Baseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation ((192)Ir: Checkmate, Cordis, Miami, Florida; (32)P: Gallileo, Guidant, Houston, Texas; (90)Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of "reference isodose length" (RIL), defined as a segment with >/=90% of reference dose at 1 mm vessel wall depth, were measured. "Safety margin" was defined as the distance between the outermost injury and outermost end of the RIL, "geographical miss" (GM) as a complete injured segment not being covered by the RIL, and "restenosis" as the percent diameter stenosis >50%. RESULTS: Baseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. CONCLUSIONS: Geographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

Beta Particles↗

Possible impact of iridium-192 source centering on restenosis rate after femoro-popliteal angioplasty and endovascular brachytherapy in Vienna-2 study.

PURPOSE: Endovascular brachytherapy (EVBT) has been proven to significantly reduce restenosis after percutaneous transluminal angioplasty (PTA). The object of this analysis was to assess the possible correlation between iridium-192 source non-centering and angiographic-determined restenosis. MATERIALS AND METHODS: A total of 113 patients with long-segment lesions of the superficial femoro-popliteal artery (SFA) were randomized to receive either PTA alone or PTA followed by EVBT in the Vienna-2 study. This analysis was performed on a subgroup of 34 out of 57 patients, who received PTA+EVBT. Angiographic restenosis was defined as lumen reduction of more than 50%. Angiograms taken immediately after PTA (34 patients) and at follow-up (25 patients) were analyzed. The distance between the vessel wall and the actual position of the source at the time of EVBT was measured (in mm) and correlated with the follow-up vessel lumen diameter. Measurements were performed at points at a distance of 10 mm from each other. The dose was determined at the luminal surface and at the reference depth of 2 mm into the vessel wall for different distances from the source. RESULTS: Among the 622 measured points, 62 (10.0%) were within restenotic areas; 560 (90.0%) were in arterial segments without proven angiographic restenosis. As far as source centering is concerned, 7.9% of restenotic points were observed when the maximum distance to the arterial wall was <3 mm and 9.6% for 4 mm, respectively. The percentage of restenotic points increased up to 15.9% when the maximum distance to the arterial wall was 5 mm and reached 22.2% when it was >5 mm. CONCLUSIONS: The proportion of restenotic points significantly increased with source non-centering. This observation was interpreted as being related to a decrease in dose at the target. When the maximum distance between the source and the vessel surface was >5 mm, the dose at the reference depth (2 mm into the vessel wall) decreased to values lower than 5 Gy.

Angioplasty, Balloon, Coronary↗