[Causes of death in amyotrophic lateral sclerosis : Results from the Rhineland-Palatinate ALS registry]. / Todesursachen bei amyotropher Lateralsklerose : Ergebnisse aus dem ALS-Register Rheinland-Pfalz.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is associated with an increased mortality. Knowledge of possible causes of death could lead to an individualization of the palliative treatment concept and result in a differentiated palliative treatment pathway. Currently, only few systematic data are available on the heterogeneity of causes of death associated with ALS. OBJECTIVE: Analysis of the various causes of death in a prospective population-based German cohort of ALS patients. MATERIAL AND METHODS: Analysis of data of the Rhineland-Palatinate ALS registry in which newly diagnosed patients who had been identified between October 2009 and September 2012 were prospectively enrolled and followed up at regular intervals. From this prospective cohort study the causes of death were elicited based on information provided by the attending physicians, family members and by means of death certificates registered by the regional health authorities in Rhineland-Palatinate. RESULTS: Out of 200 ALS patients registered 148 died between register initiation on 1 October 2009 and the end of follow-up on 30 September 2015 (78 males and 70 females, death rate 74%). The most frequent cause of death was respiratory failure as a consequence of weakness of respiratory muscles (n = 91, 61%). Less frequent causes of death were pneumonia (n = 13, 9%), terminal cachexia (n = 9, 6%) and death from cardiovascular causes including sudden death (n = 9, 6%). Cases of suicide were rare (n = 3, 2%) as were deaths due to concurrent diseases (n = 2). In 21 cases (14%) the exact cause of death could not be clarified. Differences in the causes of death only showed a tendency towards the ALS phenotype. Respiratory failure was the cause of death in all patients with a respiratory phenotype and in 78% of patients with flail arm syndrome. Despite the low number of patients (8%) with additional frontotemporal dementia (FTD) a distinct difference in causes of death between those with and without FTD could be observed. Death due to respiratory failure was less frequent in ALS patients with FTD (33% vs. 65%) while pneumonia was more frequent (27% vs. 7%). CONCLUSION: Respiratory failure was the most frequent cause of death in our cohort of ALS patients. In contrast, pneumonia and nutritional disorders played a less important role as the cause of death. The phenotypic expression of ALS might in part allow the cause of the prospective death to be predicted. Differentiation of ALS phenotypes is an important foundation for patient counseling on the process of dying to be expected and for the determination of an individual palliative concept.

Green tea polyphenols and their potential role in health and disease.

There is a growing body of evidence that plant polyphenols such as resveratrol, anthocyanins, catechins, and terpenes like taxol are effectively used in the treatment of chronic conditions including cancer, Alzheimer, Parkinsonism, diabetes, aging, etc. The link between oxidative stress and inflammation is well accepted. Thus, the mechanism of action of these natural products is partly believed to be through their significant antioxidant properties. The main constituent of green tea, with clinical significance, is epigallocatechin gallate (EGCG). It has been associated with antitumor, anti-Alzheimer, and anti-aging properties, improve redox status at the tissue level possibly preventing system level structural damage. This review focuses on EGCG and its potential therapeutic role in health and disease.

Intracerebral haemorrhage in a population-based stroke registry (LuSSt): incidence, aetiology, functional outcome and mortality.

Data on incidence of intracerebral haemorrhage (ICH) vary widely. Population-based data on predictors of ICH survival and functional outcome are rare. The Ludwigshafen Stroke Study is a prospective, population-based stroke registry which started in January 2006. All residents of the city of Ludwigshafen, Germany, who suffer from acute stroke or transient ischaemic attack are registered. Patients with first-ever primary intracerebral haemorrhage (FE-pICH) between 2006 and 2010 were included in the present analysis. Between January 1st, 2006 and December 31st, 2010, 152 patients suffered a FE-pICH. Crude and age-adjusted incidence rates per 100,000 for FE-pICH were 18.7 (95 % CI 15.9-21.9) and 11.9 (95 % CI 10.2-14.0), respectively, and remained stable over time. Case-fatality rates for FE-pICH were 27.0, 34.9 and 44.1 % at days 28, 90 and 365, respectively. In 21 patients, an (21.3 %) early do-not resuscitate-order was documented. Excluding these patients from multivariate analyses, National Institute of Health Stroke Scale (NIHSS) (OR 1.22, 95 % CI 1.08-1.36), hypercholesterolemia (OR 0.16, 95 % CI 0.05-0.55) and modified Rankin Scale (mRS) prior to stroke (OR 1.56, 95 % CI 1.06-2.3) were independently associated with risk of 1-year mortality, whereas NIHSS (OR 1.41, 95 % CI 1.20-1.66) and leukocyte count on admission (OR 1.48, 95 % CI 1.16-1.89) were independently associated with good or moderate functional outcome (mRS ≤ 3) after 1 year. Incidence of FE-ICH is in the lower range of those reported from other registries and remained stable over the observation period. Higher treatment rates for hypertension might partly account for this. Stroke severity as indicated by NIHSS was independently associated with mortality and functional outcome after 1 year. We found no association between aetiology and outcome in ICH patients.

Stroke due to atrial fibrillation in a population-based stroke registry (Ludwigshafen Stroke Study) CHADS(2) , CHA(2) DS(2) -VASc score, underuse of oral anticoagulation, and implications for preventive measures.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is amongst the most important etiologies of ischaemic stroke. In a population-based stroke registry, we tested the hypothesis of low adherence to current guidelines as a main cause of high rates of AF-associated stroke. METHODS: Within the Ludwigshafen Stroke Study (LuSSt), a prospective ongoing population-based stroke register, we analyzed all patients with a first-ever ischaemic stroke (FEIS) owing to AF in 2006 and 2007. We determined whether AF was diagnosed before stroke and assessed pre-stroke CHADS(2) and CHA(2) DS(2) -VASc scores. RESULTS: In total, 187 of 626 patients with FEIS suffered from cardioembolic stroke owing to AF, which was newly diagnosed in 57 (31%) patients. Retrospective pre-stroke risk stratification according to CHADS(2) score indicated low/intermediate risk in 34 patients (18%) and high risk (CHADS(2)  ≥ 2) in 153 patients (82%). Application of CHA(2) DS(2) -VASc score reduced number of patients at low/intermediate risk (CHA(2) DS(2) -VASc score 0-1) to five patients (2.7%). In patients with a CHADS(2) score ≥ 2 and known AF (n = 106) before stroke, 38 (36%) were on treatment with vitamin K antagonists on admission whilst only in 16 patients (15%) treatment was in therapeutic range. CONCLUSIONS: Our study strongly supports the hypothesis that underuse of oral anticoagulants in high-risk patients importantly contributes to AF-associated stroke. CHA(2) DS(2) -VASc score appears to be a more valuable risk stratification tool than CHADS(2) score. Preventive measures should focus on optimizing pre-stroke detection of AF and better implementation of present AF-guidelines with respect to anticoagulation therapy.

Curative propensity of green tea extract towards hepatic fibrosis induced by CCl(4): A histopathological study.

Hepatic fibrosis constitutes a serious insult to the liver, with a substantial negative impact on the quality of life of such patients worldwide. It is a consequence of severe liver damage and occurs as the result of several factors. Chronic alcoholism is the most common cause. Fibrosis also results from chronic viral hepatitis and autoimmune hepatitis. Prolonged exposure to environmental toxins such as carbon tetrachloride (CCl(4)) can also lead to fibrosis. In the present study, the hepato-protective effects of green tea extract (GTE) on hepatic fibrosis in a rat liver CCl(4)-induced fibrosis model were examined histologically, 3-dimensionally and biochemically. GTE was prepared from dried green tea leaves and lyophilized. Male albino rats (n=20) weighing 200-250 g were divided into four groups: GI, control; GII, administered 50 mg/kg GTE dissolved in physiological saline daily for four weeks; GIII, administered 40% CCl(4) (1 ml/kg body weight) by subcutaneous injection daily for four weeks; and GIV, treated as GIII, followed by 50 mg/kg GTE dissolved in physiological saline daily for 4 weeks. Histology and 3-dimensional scanning electron microscopy showed hepatic fibrosis with intermingled fibers located between cells in the liver tissues of the CCl(4)-treated rats. Fibrotic lesions virtually disappeared after four weeks of treatment with GTE, returning the architecture of liver tissue back to its normal state. Also, the levels of the hepatic enzymes alanine aminotranferase and aspartate aminotransferase returned to their normal levels after treatment with GTE. The rats were found to regain their normal body weight and their fur color, which had faded due to weight loss. The autopsy results showed the animal liver returning to normal shape and color. Thus, green tea extract is a potent treatment for hepatic fibrosis caused by CCl(4) in this animal model.

Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen Stroke Study, a population-based stroke registry.

BACKGROUND: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. RESULTS: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 ± 12.6 years) than men (n = 299; 69.7 ± 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20-1.56) than in women (1.12; 95% CI 0.97-1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and 'probable atherothrombotic stroke' (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p < 0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p = 0.024) was significantly more common in men than in women. Overall, 1-year survival was not different between both sexes; however, a significant age-sex interaction with higher mortality in elderly women (>85 years) was detected. CONCLUSIONS: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men.

Analyzing Thorough QT Study 1 & 2 in the Telemetric and Holter ECG Warehouse (THEW) using Hannover ECG System HES : A validation study.

Following the ICH E14 clinical evaluation guideline [1], the measurement of QT/QTc interval prolongation has become the standard surrogate biomarker for cardiac drug safety assessment and the faith of a drug development. In Thorough QT (TQT) study, a so-called positive control is employed to assess the ability of this study to detect the endpoint of interest, i.e. the QT prolongation by about five milliseconds. In other words the lower bound of the one-sided 95% confidence interval (CI) must be above 0 [ms]. Fully automated detection of ECG fiducial points and measurement of the corresponding intervals including QT intervals and RR intervals vary between different computerized algorithms. In this work we demonstrate the ability and reliability of Hannover ECG System (HES(®)) to assess drug effects by detecting QT/QTc prolongation effects that meet the threshold of regulatory concern as mentioned by using THEW database studies namely TQT studies one and two.

Cyto-protective and immunomodulating effect of Curcuma longa in Wistar rats subjected to carbon tetrachloride-induced oxidative stress.

A comparison of crude curcuminoid extract and purified curcumin was made to evaluate hepato- and immunoprotective effect of Curcuma longa (turmeric) Zingiberaceae. Carbon tetrachloride (CCl4) induced cellular hepatic damage was evaluated by transmission electron microscopy, hepatic enzymes and thiobarbituric acid reactive species (TBAR) values. A selective cytolytic effect of CCl4 was observed among immature (PNA+) thymocytes and peripheral helper (CD4+) T lymphocytes in spleen and was paralleled by a significant reduction in CD25, CD71 and Con A receptor expression. Treatment with curcuminoid crude extract at two different doses, showed a significant cellular recovery among hepatocytes, which was reflected in a reduction of hepatic enzymes and TBAR values. A significant restoration of lymphocyte viability and CD25, CD71 and Con A receptor expression in both immature (PNA+) thymocytes and splenic helper (CD4+) T lymphocytes was observed. Turmeric crude extract, at both low and high dose, was found to be more efficient as compared to purified curcumin.

Analysis of responses of Long Beach, California residents to the Smoke-free Bars Law.

OBJECTIVES: We investigated survey responses to the Smoke-free Bars Law by residents of Long Beach, California (population 460,000), a city that reflects the state's diverse population. The research specifically aimed to determine: (1) residents' approval for the 1998 California Smoke-free Bars Law when it was implemented; and (2) changes in approval between baseline and 2-year follow-up. Data were also assessed for the demographic characteristics of the respondents and whether the respondents were self-acknowledged smokers or non-smokers. STUDY DESIGN: A random telephone survey was conducted in 1998 and 2000 in Long Beach to determine the degree of community support for the 1998 state law that prohibited smoking in all workplaces including alcohol-serving establishments. The numbers analysed were 784 in 1998 and 1237 in 2000. METHODS: Statistical analyses used in this research included univariate frequency distributions and logistic regression for 1998 and 2000. RESULTS: The major findings were as follows. Overall community approval for the 1998 state law increased from 65.2% in 1998 to 72.6% in 2000. Over this period, the rate of approval by smokers increased from 20.6% to 37.1%, and the rate of approval by non-smokers increased from 74.5% to 80.3%. CONCLUSIONS: The general public in a large city in California strongly approve of the prohibition of smoking in all indoor public places. This strong endorsement has major public health implications.

CoQ9 potentiates green tea antioxidant activities in Wistar rats.

Green tea (Camellia sinensis), and CoQ(9 )when given to Wistar rats produced a partial reversal on reserpine induced oxidative stress and liver damage. Green tea, with its abundant polyphenol (-)Epigallocatechin 3-gallate (ECGC) and other catechins, is known for its antioxidative characteristics influencing lipid metabolism. Ubiquinone, abundant in heart muscle, is also a potent antioxidant with known effects in numerous pathologies. However the combined effect of ECGC and ubiquninone has not been reported. In the present study we found that green tea extract, when given in combination with CoQ(9) to Wistar rats subjected to oxidative stress, showed a statistically significant antioxidative effect. Liver cholesterol level in rats receiving combination treatment was also significantly lower than control or rats receiving green tea extract alone. Reserpine induced liver damage in Wistar rats was also partially reversed by a treatment of green tea extract when combined with CoQ(9). These results may have important clinical implications and may be extrapolated for the treatment of patients suffering from liver damage due to hepatitis B/C or liver cirrhosis.

Public opinion analysis regarding the uses of master settlement agreement (MSA) funds.

OBJECTIVES: In the present research, we assessed the relationship between characteristics of the residents of Long Beach, California, a typical city in America, and their opinions regarding the uses of master settlement agreement (MSA) funds. METHODS: The statistical analyses used in the present research included univariate frequency distributions, cross-tabulations, and classification and regression trees. RESULTS: The results indicate that the majority of Long Beach residents share the opinion that the MSA funds should be allocated to health programmes. They do not, however, feel that these funds need to be earmarked solely for smoking prevention or cessation. CONCLUSIONS: Due to state budget deficits, legislators may strongly advocate for the MSA funds to be used for non-health purposes. Our findings provide support for community advocates who wish to bring the current uses of MSA funds and tobacco taxes to the forefront of national and international public debate.

Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors.

Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.

Hepatotoxicity induced by the anti-oxidant food additive, butylated hydroxytoluene (BHT), in rats: an electron microscopical study.

The anti-oxidant food additive, butylated hydroxytoluene (BHT), was fed to Sprague-Dawley rats at three concentrations: 0.2%, 0.4% and 0.8% for periods of 6, 12, 18 and 24 weeks, and the results were compared with corresponding groups treated with a potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) groups, with olive oil, and with untreated control groups. BHT resulted in a significant increase in liver weight. The liver cells presented gradual vacuolization, cytoplasmic disintegration, "moth-eaten" appearance, ballooning degeneration, hepatocellular necrosis, aggregation of chromatin material around the periphery of the nuclear envelope, SER proliferation, RER clumping with broken cisternae, withered and autolyzed mitochondria, augmentation of lipid droplets and glycogen depletion. On the other hand, there was no sign of tumorigenicity. Whether or not BHT acts as a carcinogen in long-term administration may depend not only upon the organ system examined, but also on the strain of the animal used.

Cytotoxicity of Kuwait weathered lake crude oil on rat hepatocytes: a histological and ultrastructural study.

In the present study, the cytotoxic effects of Kuwaiti weathered crude oil and a potent carcinogen (DMBA) on rat liver cells were examined by light and electron microscopy at each of 4 sampling periods after the start of low dosing (0.5 and 0.2 mg/kg) of feed. Such effects were compared with those of olive oil and uncontaminated food-exposed controls. The results confirm a pronounced cell damage which statistically not significant (p < 0.05). In crude oil, the organelle changes were variable and highly comparable to that of DMBA. The nuclei were mostly disintegrated while the cell showed demarcation of cytoplasmic vacuolization, lipid augmentation, and mitochondrial aberrations. The latter showed a remarkable association with the rough endoplasmic reticulum and lipid droplets, and appeared as decayed and diffused structures within the cell matrix. There was no comparable changes in the hepatocytes of animals fed with uncontaminated food except for the formation of lipid droplets in the olive oil-fed groups. Although the animals food was contaminated with Kuwaiti weathered oil formed in 1991 were exposed to extreme seasonal temperatures, yet the residues of such oil led to severe histopathological alterations in the liver cells which were similar to those of DMBA-treated cells. There is the need to pay attention to potential hazardous effects of the crude oil on environments.

Distention of the lateral intercellular spaces (LIS) in the proximal tubule cells of the non-stenosed kidney of the 2K-1C Goldblatt model of hypertension as evidence of pressure diuresis.

This study shows the development of two major deformities in the non-stenosed kidney of the 2K-1C Goldblatt model; namely the widening of the LIS and the enlargement of the basilar interdigitations of the proximal tubule cells. These deformities were much less in the 2K-1C animals treated with the angiotensin I converting enzyme inhibitor (AICEI) cilazapril. From these findings it is suggested that the non-stenosed kidney is operating under the diuretic effect of the elevated systemic blood pressure (SBP) via an increase in the renal interstitial hydrostatic pressure (RIHP). Therefore, the AII antidiuretic effect is masked by the diuretic effect of the elevated SBP. The suggested rise in urine output fits well with the idea that kidneys lose water and sodium when SBP increases enormously. Therefore, in this model of hypertension, the non-stenosed kidney tries to lower SBP by losing water and sodium, an excretion behavior which is opposite to that of the stenosed kidney. Thus, the rise in SBP in this model is probably due to an increase in the vascular peripheral resistance rather than fluid accumulation.

Presence of cerium-cytochemical reactions of glomerular phosphatases of normal gerbil Meriones crassus: an ultrastructural localization study.

Phosphatase cytochemical activity in the normal glomerulus of the desert gerbil Meriones crassus was demonstrated using cerium ions as capturing agents. Three major enzymes have been recognized: sodium-potassium adenosine triphosphatase (Na(+)-K(+)-ATPase), alkaline phosphatase (ALPase) and acid phosphatase (ACPase). However, cytochemical staining for these markers to map their localizations and distributions reveal a high positivity of Na(+)-K(+)-ATPase. This appeared as uniform dense precipitates surrounding the glomerular basement membrane (GBM) and the plasma membranes of the epithelial and endothelial cells of the glomerular layers. Negligible ALKase reaction product being over the glomerular epithelia including the GBM. In contrast, the cytochemical profiles of ACPase was unusual, with dense reaction products extensively covering the endoplasmic reticulum at the region of Golgi apparatus products lysosomes (GERL) complex, including its cisternal and tubular elements and the lysosomal-vacuolar apparatus of the glomerular epithelial cells. All other subcellular organelles showed no activity. For Na(+)-K(+)-ATPase, the reaction product was successive when acetate buffer (as decalcifying agent, pH 5.0) was used. This reaction was still seen when a medium containing levamisole was used. Cytochemical controls for all enzymes were incubated in substrate-free media including those using levamisole as an inhibitor of ALPase. The data presented, which is reported for the first time, is not an attempt to determine the contribution of the selected phosphatases in the glomerular physiology and pathology. Such findings may, nevertheless, have functional implications in the fact that these markers may be involved in the ultrafiltration and other metabolic activities of the glomerulus at the molecular and/or cellular level. In addition to earlier morphological and recent histochemical work, the present study updates and recognizes information to be used as a baseline to which the gerbil model can now be employed to investigate the behavioural adaptations of the desert rodents.

MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in healthy volunteers: in vivo studies with positron emission tomography.

OBJECTIVE: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. METHODS: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined with positron emission tomography (PET) with [11C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide, and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7, one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning dose on day 7. RESULTS: PET showed a high degree of binding of [11C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point. In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about 4 h. CONCLUSION: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination of dosing intervals.

Porous balloon delivery of low molecular weight heparin in the dog coronary artery.

UNLABELLED: The aim of this experimental study was to assess the safety of local delivery of low molecular weight heparin via a porous balloon in the canine coronary artery. In 16 mongrel dogs, percutaneous transluminal coronary angioplasty was performed. In addition, eight of the dogs were given 4 ml Clivarin (1500 IU) delivered locally into the coronary artery immediately after dilatation. The animals were killed after 3 or 14 days. In the animals with local administration, the results of histopathology after 3 days showed the findings to be heterogeneous with marked disruption of the internal elastic lamina in all animals, and varying degrees of medial haemorrhage, medial necrosis, perivascular haemorrhage and signs of myocardial necrosis. Similar changes, but of lesser severity, were present in the animals treated with balloon dilatation only. After 14 days, the severity of vascular and perivascular alterations (medial haemorrhage, perivascular haemorrhage, thrombus formation) was significantly lower in the local delivery group (P < 0.05), but disruption of the internal elastic lamina, as a marker of the initial trauma, was present in all the animals. The presence of residual intracoronary thrombus was only seen in the PTCA group without local delivery. CONCLUSIONS: In this safety study, both groups showed pronounced alterations in the vessel wall 3 days following percutaneous transluminal coronary angioplasty. This changed 14 days following percutaneous transluminal coronary angioplasty when intramural injection of Clivarin resulted in a marked decrease of residual thrombus and medial as well as perivascular haemorrhage. Although the additional vessel trauma by the drug delivery technique did not result in increased complications, a careful approach with this potentially harmful procedure is essential.