Search

Author(s): Chang, L; Chey, WD; Drossman, D; Losch-Beridon, T; Wang, M; Lichtlen, P; Mareya, S | Abstract: BackgroundLubiprostone (8 μg b.d.) received US Food and Drug Administration (FDA) approval in 2008 for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in women aged ≥18 years. In 2012, the FDA issued new guidance for IBS-C clinical trials, recommending a composite endpoint incorporating both abdominal pain and stool frequency.AimIn a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double-blind, randomised trials of lubiprostone in patients with IBS-C.MethodsIncluded patients had a baseline spontaneous bowel movement (SBM) frequency l3/week and abdominal pain or bloating ratings ≥1.36 on a 5-point scale [0 (absent) to 4 (very severe)]. Responders (composite endpoint) had a mean pain reduction ≥30% compared with baseline, and an increase from baseline of ≥1 SBM/week for ≥6 of the 12 treatment weeks. Lubiprostone effects on abdominal pain alone were also evaluated, as were bloating alone and in a composite endpoint with stool frequency.ResultsIn pooled data, 325 patients received lubiprostone and 180 received placebo. Rates of response were higher with lubiprostone vs. placebo for the composite endpoint of improved pain and stool frequency (26.3% vs. 15.3%, respectively; P = 0.008) and the composite endpoint of improved bloating and stool frequency (23.8% vs. 12.6%, respectively; P = 0.012). Response rates were also higher with lubiprostone vs. placebo for abdominal pain alone (P = 0.005) and bloating alone (P = 0.012).ConclusionLubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency.

Placenta growth factor (PlGF) is a mitogen for endothelial cells that can potentiate the growth and permeabilizing effects on endothelium of vascular endothelial growth factor. Here we report that hypoxia induces the expression of both PlGF mRNA and protein in immortalized/transformed mouse embryonic fibroblasts (mEFs) and in NIH 3T3 cells. Importantly, the magnitude of the induction of PlGF expression by hypoxia is enhanced by the presence of oncogenic Ras. To investigate the transcriptional component of hypoxia-inducible PlGF expression, we cloned and sequenced a 1350-bp fragment of the 5'-flanking region of the mouse gene. Analysis of the promoter region indicated the presence of putative consensus sequences for known hypoxia-responsive regulatory sites, including metal response elements and Sp1-like sites. In the present study, we show that the induction of PlGF expression by hypoxia is dependent on the presence of the metal response element-binding transcription factor 1 (MTF-1). Thus, in mEFs with targeted deletions of both MTF-1 alleles, hypoxia-induced increases of PIGF mRNA and protein levels were greatly attenuated compared with those in wild-type mEFs. Moreover, transient transfection of a PlGF promoter reporter gene into NIH 3T3 cells resulted in hypoxia-responsive transcriptional activation of the reporter. Finally, ectopic expression of MTF-1 resulted in increased basal transcriptional activity of a PlGF promoter reporter. Together, these findings demonstrate that the PlGF gene is responsive to hypoxia and that this response is mediated by MTF-1. It remains to be determined whether this activation is the result of direct and/or indirect transcriptional activation by MTF-1. The stimulatory effect of oncogenic Ras on the induction of PlGF expression in hypoxic cells suggests that PlGF could be an important proangiogenic factor in the tumor microenvironment.

Introduction Constipation affects millions globally; however, many patients are dissatisfied with currently-available laxative treatments, with most interested in access to other treatment options 1 . Lubiprostone (24 mcg BID) has been shown to be effective and well-tolerated in patients with refractory constipation. Methods Post-hoc analysis was conducted to evaluate whether lubiprostone provides relief in patients who are refractory or lacking adequate relief from other common constipation therapies. Pooled patient and medication data from two pivotal trials were assessed. Patients with a history of constipation despite the use of constipation medication during the 90 days prior to initiation of study medication were included. Response rates and symptomatic improvements in this subpopulation of refractory patients were analysed based on treatment assignment in the clinical trial: lubiprostone (24 mcg BID) or placebo. Analysis was performed on the whole and by the class of prior medication usage. Patients were considered full responders if they achieved ≥4 spontaneous bowel movements (SBMs)/week. Patients achieving ≥3 but Results Full response to treatment ranged from 52.8 to 67.2% across the 4 weeks of treatment, as compared to 32.3% to 47.4% for placebo patients. For patients who were moderate responders, response rates increased to 64.8–80.0% among the lubiprostone treatment group compared to only 46.6–57.9% of placebo patients. Lubiprostone produced a significant and full response over placebo, respectively, among the refractory patients who previously took contact laxatives 50.9–64.9% vs. 21.3–42.6%; PEG solutions 57.5–75.0% vs. 32.5–52.5%; or enemas 50.0–71.4% vs. 23.3–50.0%. For symptoms of constipation such as stool consistency and straining, lubiprostone treatment resulted in statistically significant improvements compared to placebo at each study week (p≤0.001). In particular, lubiprostone statistically significantly improved overall stool consistency among patients who previously used contact laxatives (p≤0.001), enemas (p≤0.007) or PEG solutions (p≤0.003) at all treatment weeks. Statistically significant improvements in straining were seen at all treatment weeks in patients who previously used PEG solutions (p≤0.018). Conclusion Given the statistically significant response to lubiprostone in patients refractory to other constipation therapies, lubiprostone may be a helpful addition to the armamentarium for patients suffering from chronic idiopathic constipation. Disclosure of Interest None Declared. Reference Muller-Lissner et al. Aliment Pharmacol Ther 2013; 37(1):137–145.

Introduction Constipation affects millions globally and may require chronic treatment. In 24- and 48-week trials, lubiprostone demonstrated safety and efficacy in long-term treatment of adults with chronic idiopathic constipation. Analyses of lubiprostone’s (24 mcg BID) efficacy in age, gender and race subgroups were performed. Aims and Methods Pooled data from three Phase 3 open-label safety studies were reviewed to analyse efficacy in the following subpopulations: non-elderly ( Results In the non-elderly and elderly, lubiprostone improved constipation severity (p≤0.0001) each week beginning at Week 1 and continuing through Week 48. Among males and females, lubiprostone improved (p≤0.0001) constipation severity each week with similar findings (p≤0.0001) for non-whites and whites, For abdominal discomfort, significant changes were seen at all weeks in the non-elderly (p≤0.0001) and for all weeks in the elderly (p≤0.0001 to p = 0.0150) except Week 8 (p = 0.0530). Among the genders, improvements occurred at all weeks in males (p≤0.0001 to p = 0.0220) and in females (p≤0.0001). By race, improvements occurred at all weeks among non-whites (p≤0.0001 to p = 0.0020) and among whites (p≤0.0001). Significant changes in abdominal bloating were seen in the non-elderly (p≤0.0001) and for the elderly (p≤0.0001 to p = 0.0180) at all weeks. Abdominal bloating improved at all weeks for males (p≤0.0001 to p = 0.0010) and females (p≤0.0001). For non-whites and whites, abdominal bloating improved (p≤0.0001) at all weeks. Conclusion Lubiprostone demonstrated long-term efficacy through an overall improvement in constipation severity for up to 12 months regardless of age, gender, or race. Similarly, improvements were noted in abdominal bloating and abdominal discomfort for both race and gender subpopulations along with some significant and positive trend for improvement in the age group analyses. Disclosure of Interest None Declared.

Introduction Constipation is a common condition affecting millions globally. Lubiprostone has demonstrated safety and efficacy in treating adults with chronic idiopathic constipation. Through an analysis of the subgroups of two Phase 3 studies, the efficacy of lubiprostone based on factors such as age, gender, and race was reviewed. Aims and Methods Combined data from two Phase 3 well-controlled studies were used to analyse the following subpopulations: non-elderly ( Results Among non-elderly patients, lubiprostone produced a greater increase (p≤0.001) in SBM frequency each week over placebo. Statistically significant increases were observed in the elderly (p = 0.0188 to p = 0.0268) at each week except Week 2 (p = 0.0806). Statistically significant improvements were noted in females (p≤0.001) at all weeks and in males at all weeks (p = 0.0115 to p = 0.0500) except Week 3 (p = 0.0758). For non-whites (p = 0.0003 to p = 0.0021) and whites (p≤0.001), statistically significant increases in SBM frequencies were reported at all weeks. Table 1 shows the weekly change in SBM frequency for each group. Stool consistency was improved with lubiprostone in the non-elderly (p = 0.0172 to p = 0.0441) and the elderly (p≤0.001) at all weeks. Straining was also improved with lubiprostone treatment at all weeks in non-elderly patients (p≤0.001), with similar improvement trends observed in the elderly. Stool consistency and straining were statistically significantly improved with lubiprostone at all weeks (p≤0.001) in females. A similar trend was observed for males but did not achieve statistical significance at all weeks. Lubiprostone improved stool consistency at all weeks in whites (p≤0.001) and non-whites (p≤0.0001 to p = 0.0006). Straining was improved at all weeks for whites (p≤0.001) and non-whites (p≤0.0001 to p = 0.0144). Conclusion Treatment with lubiprostone resulted in increased SBM frequencies and improvement in related symptoms in patients with chronic idiopathic constipation regardless of age, gender, or race. Disclosure of Interest None Declared.

Introduction Lubiprostone, a novel ClC-2 activator, has been shown to be efficacious and well-tolerated by patients with chronic constipation in short- and long-term clinical trials. To better characterise the most frequent adverse events (AEs) associated with the use of lubiprostone 24 mcg BID, we examined pooled results of patients enrolled in Phase 2 and 3 trials of 3 to 48 weeks’ duration. Methods Data for all safety-evaluable patients were pooled and compared between treatment groups (placebo vs lubiprostone 24 mcg BID). Nausea, headache, and diarrhoea AEs were analysed in terms of severity, duration, frequency, action taken (eg, drug withdrawn, dose reduced), and outcome. In addition, nausea-related variables were explored in subpopulations of elderly (≥65 years of age) and male patients. Results The pooled population included 1113 lubiprostone and 316 placebo patients. Approximately 16% were elderly and 13% were male. At least 1 AE occurred in 79.1% of lubiprostone patients, which included 31.1% with nausea, 13.2% with headache, and 13.2% with diarrhoea. At least 1 AE occurred in 39.6% of placebo patients, which included 5.1% with nausea, 6.6% with headache, and 0.9% with diarrhoea. Of those lubiprostone patients who experienced nausea, 88.7% reported nausea to be mild or moderate in severity. Overall, 74.5% of nausea events reported by lubiprostone patients were intermittent, and the median durations of nausea events were 12 and 7.5 days for lubiprostone and placebo patients, respectively. Notably, mean incidences of nausea per patient were 1.3 and 1.0 for lubiprostone and placebo patients, respectively. With regard to action taken, 64.1% of nausea events required no change in treatment regimen, and 9.6% of events resulted in dose reduction. Nausea was less prevalent in subpopulations, occurring in only 18.8% and 8.2% of lubiprostone elderly and male patients, respectively, compared with 34.5% of female patients. Similarly, the majority of lubiprostone patients experiencing headache and diarrhoea had mild-to-moderate symptom severity (89.8% and 82.3%, respectively). Furthermore, headache and diarrhoea events in lubiprostone patients were mostly intermittent (64.2% and 74.0%, respectively), and the median duration of these events were 9 and 4 days, respectively. Discontinuation rates due to nausea, headache, and diarrhoea were 8.7%, 3.7%, and 2.2%, respectively. Conclusion Nausea, headache, and diarrhoea associated with lubiprostone use are generally mild to moderate in severity, intermittent, and limited in duration. Disclosure of Interest None Declared.

In recent years follow-up trials on coronary artery disease with angiographic end points analyzed quantitatively have gained increasing relevance and popularity. There is no consensus, however, on the method of calculation of progression or regression from multiple angiographic projections. Therefore the influence of the selection of angiographic projections on the outcomes of such trials was investigated with the data of the International Nifedipine Trial on Antiatherosclerotic Therapy. In 348 patients with coronary artery disease, repeated coronary angiograms were compared in multiple identical angiographic projections. Changes in angiographic parameters were averaged over the 1063 stenoses analyzed. Five methods of evaluation of multiple projections in the individual stenoses were applied, resulting in different extents of overall progression, or even regression of coronary artery disease (p0.01). It is concluded that in quantitative coronary angiographic follow-up trials changes should be averaged over all angiographic projections available for a stenosis to avoid overestimation of progression or regression.

The vascular responses to 17 beta-oestradiol were examined in 23 postmenopausal women (59 +/- 7 years [mean +/- SD]) using a placebo-controlled double-blind crossover design. All women received 1 mg 17 beta-oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60-80 min after application of verum or placebo as well as 10-30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4 +/- 4.1% of basal, P < 0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 +/- 2.1%). The blood flow rate increased significantly after oestradiol application (+30 +/- 28%, P < 0.05 vs. basal and P), but not after placebo (+11 +/- 21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17 beta-oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases in postmenopausal women.

We compared embolectomy (when available) with thrombolysis in patients with shock and massive pulmonary embolism. 13 patients were operated on, 10 (77%) of whom survived. The inferior vena cava was routinely clipped. The 24 medically treated patients were given alteplase until systemic and pulmonary artery pressures stabilised and heparin thereafter; 16 (67%) survived. Major haemorrhage occurred in 28% of medically treated patients, but was not fatal. 1 patient had a small cerebral haemorrhage that resolved without drainage. One-fifth of the medical group had a re-embolism, which suggests that temporary caval umbrellas are indicated in medically treated patients. Thrombolysis may provide a life-saving option and a randomised trial is warranted.

Tolerance of a New Non-ionic Contrast Medium during Heart Catheterization The new non-ionic contrast medium iomeprol (CAS 78649-41-9) was investigated for adverse reactions and diagnostic quality in 75 patients undergoing heart catheterization. Blood pressure and ECG were continuously registered. The patients were asked for subjective complaints by using a standardized questionnaire. Experienced cardiologists assessed the diagnostic quality of the angiograms. With iomeprol neither fatal nor severe reactions were observed. The dye had only little influence on diastolic and systolic blood pressure; heart rate was not significantly influenced. Minor and partly moderate adverse reactions all being completely reversible were observed in 14 patients (18.7%). One patient complained of strong heat sensation after dye injection into the left ventricle. The diagnostic quality of the angiograms allowed to make a definitive diagnosis in all cases. Thus, iomeprol proved to be a suitable and safe contrast medium for heart catheterization.

Intracoronary stenting was designed to handle acute vessel closure after balloon angioplasty and to reduce the rate of restenosis. In three cardiology centers the implantation of 200 balloon-expandable Palmaz-Schatz stents was attempted in 179 patients. The implantation was successful in 170 patients (95%). During bail-out implantation for acute vessel closure or symptomatic dissections after balloon angioplasty, implantation succeeded in 60 (91%) of 66 attempted patients, who recovered immediately from ischemia. Three patients received emergency bypass surgery and three patients were kept on medical therapy. Restenosis after 4 to 6 months, defined as50% diameter reduction, was documented angiographically in 18 (15.3%) of 118 presently controlled patients. Patients with single stent implantation (n = 106) presented a late restenosis rate of 10.4% in contrast to patients with multiple stent implantation (n = 12), who presented a restenosis rate of 58.4%. Similar results on restenosis were found for patients with elective and bail-out stent implantation. Acute thrombotic stent occlusion occurred in three patients (1.8%) during the first 24 h after stenting. Three to 9 days after implantation subacute stent thrombosis occurred in 15 (8.8%) of 170 patients. Despite adequate therapy including thrombolysis, balloon angioplasty or emergency bypass surgery in 14 of 15 patients Q-wave myocardial infarction was documented in six patients and non Q-wave myocardial infarction in five patients. The following parameters were identified as risk factors for the development of subacute stent thrombosis: bail-out indication, unstable angina, type C lesion, stenosis length1.5 cm, plaque area3.5 mm2, symptomatic dissection after balloon angioplasty, incomplete wrapping of the dissection after stenting and residual distal vessel irregularities after stenting. Bleeding complications occurred in 12.4% of the patients and were related to the anticoagulation and antiaggregation therapy. In conclusion, the implantation of Palmaz-Schatz stents is an excellent bail-out device to treat acute vessel closure or symptomatic dissections after angioplasty. Elective and bail-out single stent implantation is associated with a reduced rate of restenosis when compared to conventional balloon angioplasty. At present, subacute stent thrombosis and bleeding complications are the major limitations with a combined rate of 15.9%.

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

In 41 consecutive patients with 49 stenoses of aorto-coronary venous bypass (ACVB) grafts percutaneous transluminal angioplasty (PTA) was attempted. PTA was successful, i.e., the percent area stenosis was reduced by greater than 20% to less than 70% (quantitative measurement with a precision magnifying lens from two orthogonal angiographic views) in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92%) with 42 stenoses control coronary angiography was performed after a mean interval of 189 +/- 186 days. Recurrence, defined as an increase of percent area stenosis to greater than or equal to 70%, was found in nine stenoses (21%) of nine patients (26%). Recurrence correlated with a stenosis length greater than 10 mm before PTA (5/8 vs 4/32 stenoses: p less than 0.01). In recurrent stenoses, the average diameter of the grafted native coronary artery was significantly smaller than in recurrence-free stenoses (1.92 +/- 0.52 mm vs 2.45 +/- 0.50 mm; p less than 0.01). Clinical data were collected from all 38 patients with successful PTA after an average of 30 +/- 17 months following PTA. In this interval, 11 patients had undergone re-angioplasty and eight patients were re-operated; in addition, there were three cardiac deaths. In the 27 surviving patients without re-operation (71%), angina pectoris had improved from a mean of 3.0 +/- 0.7 before PTA to 1.8 +/- 1.0 (CCS-classification) (p less than 0.001). In 19 of the 27 patients (70%) the exercise stress test was negative, in contrast to only three patients (11%) before PTA. Thus, in the majority of patients PTA of ACVB-graft stenoses improves quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

A new method for quantifying regional variations in extravascular lung water (rELW) has been developed. The positron source 15O (T1/2 = 2.0 min.) was provided as H215O 'on line' by constant intravenous injection. Tomographic images (PET) of the water distribution were obtained during equilibrium. The distribution of blood volume was obtained by marking erythrocytes (carboxyhaemoglobin) using a bolus inhalation [C-11)-CO; T1/2 = 20.4 min). Absorption is calculated from transmission tomography. The rELW is defined as: total lung water minus intravascular space. The method was carried out in five intubated and anaesthetised dogs before and after induction of pulmonary oedema with oleic acid (0.06 ml./kg.). Mean ELW (PET) rose from 0.13 +/- 0.02 g./cm.3 to 0.24 +/- 0.04 g./cm.3. There was good correlation with a simultaneously performed thermo-dye method (7.1 +/- 1.3 ml./kg. KG to 13.3 +/- 1.9 ml./kg. KG; r = 0.94). Gravimetric estimations resulted in 13.7 +/- 2.6 ml./kg. KG. The development and distribution of the pulmonary oedema was non-homogeneous and varied regionally.

Ziele der Bypass-Chirurgie (BPCH) sind die Verbesserung der Angina pectoris (AP), der Leistungsfdhigkeit, der LV-Funktion sowie der Prognose der AP. Neuere Statistiken deuten auf eine sign. Besserung der letzteren nach BPCH hin, vor allem bei 2- and 3-Gefaserkrankungen. Primdre Indikation stellt nach wie vor die schwere AP mit Leistungseinbuse dar, prognostische Aspekte konnen jedoch mitbestimmend sein. Die Zone regionaler Ischdmie sollte durch LV-Angiographie unter Stress sowie regionale Flusmessungen (Szintigraphie etc.) abgegrenzt, die „kritische” Stenose exakter objektiviert werden.

Myocardial blood flow (MBF) and LV dynamics were studied under exercise (bicycle ergometry) before and after sublingual administration of Isosorbiddinitrate (ISDN) in 20 patients with angiographically severe coronary disease. Before ISDN, exercise was accompanied by a 92% increase in MBF (Xenonresidue detection technique) and a 38% decrease in total coronary vascular resistance (TCVR) (p

36 patients with 68 aorto-coronary venous bypass grafts (45 of which were angiographically patent) were examined via DSA (DV12V, serial mode, Philips) and angiography. Imaging was triggered via R waves, and effected in RAO 30 degrees, LAO 60 degrees, and AP projection. 63 of the 68 grafts were correctly detected (92.7%). Two anterior interventricular branch grafts (RIVA = ramus interventricularis anterior) were not visualised via DSA (95.6% sensitivity). One graft each to the RIVA, to the right coronary artery (RCA), and to the posterior branch of the lateral cutaneous branches of intercostal arteries (PLA), were falsely found to be patent (87% specificity). Grafts were visualised in full length. In some cases morphological changes of the walls were also visible.

The effects were investigated in rats of unilateral renal ischemia, adrenalectomy and varying doses of cortexone on the development of hypertension and on the content of pressor substances in the kidney. Adrenalectomy prevented the hypertension which follows unilateral clamping of the renal artery when a life maintaining dose of 0.1 mg cortexone acetate was injected daily. However, administration of 75 mg cortexone in the form of implants restored but did not enhance the characteristic hypertensive response to renal ischemia. The characteristic distribution of renal pressor material, being normal in the clamped and diminished in the contralateral kidney, was no longer observed after adrenalectomy when only small doses of cortexone were given but was still evident when excess cortexone was given. Overdosage with cortexone without clamping a renal artery led only to a moderate reduction of pressor material in both kidneys while in animals with unilateral renal ischemia the pressor material (renin?) in the contralateral kidney disappeared completely. Clamping the renal artery prevented the diminution of pressor material in the ipsilateral kidney which otherwise occurs under overdosage with cortexone in the normal animal.

Es werden die klinischen und angiographischen Aspekte bei 250 mit der selektiven Technik angiographierten Patienten analysiert. Bei 165 Patienten mit pathologischem Angiogramm waren die Risikofaktoren, Angina pectoris und Infarktanamnese eindeutig gehauft, wobei die beiden letzteren in der grosen Mehrzahl mit schweren Lasionen (subtotalen R. ant. desc., R. diag., R. circumfl. sin.) und in der Regel drei bis vier Aste befallen waren. Die Gegenuberstellung von Ekg resp. Vektorkardiogramm und Anamnese zeigt, das der letzteren mindestens ein ebenso groser Grad diagnostischer Treffsicherheit zukommt. Auf die Problematik des Arbeitsversuches im Vergleich mit der Angiographie wird hingewiesen. Zahl und Schweregrad der Verschlusse, ihre Lokalisation und Zahl der pro Patient betroffenenen Koronaraste sowie auch die Haufigkeit reparativer Vorgange (vor allem bei totalen Stenosen) und deren eventuellen prognostischen Implikationen werden eingehend diskutiert. Die in der vorliegenden Untersuchung mit der selektiven Angiographie gemachten Erfahrungen erweisen sich im Vergleich zu postmortalen Studien, aber auch mit der gleichen Technik gemachten Beobachtungen an einem anderen Krankengut (Sones), als sehr zuverlassig. — Die im Anschlus an die Koronarographie bei 100 Patienten durchgefuhrte Angiographie des linken Ventrikels erganzte das Koronarogramm wesentlich, indem in der uberwiegenden Mehrzahl der Falle mit positivem Koronarbefund auch eine Abnormitat des linken Ventrikels (umschriebenes oder ausgedehntes Aneurysma, Dyskinesien der Wand) gefunden wurde. — Diagnostische und prognostische sowie epidemiologische Implikationen werden abschliesend eingehend diskutiert.

Eine Uberprufung der 24 autolenkenden zurcherischen Schrittmacher-trager (Gesamtfahrpraxis circa 700000 km) zeigt eine gute Fahrbewahrung ohne nachweisbare Verkehrsgefahrdung durch das Herzleiden. Unser Ergebnis stimmt uberein mit ahnlichen Untersuchungen in Stockholm und in Hamburg [4, 13]. Ein generelles Fahrverbot bei dieser Krankengruppe wird deshalb abgelehnt; vielmehr mus jeder Schrittmachertra ger individuell beurteilt werden.

Perfusion scintigrams with Technetium-labeled microspheres were performed in 60 patients undergoing selective coronary angiography. The scintigrams were analyzed semiquantitatively with the aid of a computer. In addition, angiograms were quantitated with regard to proximal obstructions as well as regional wall changes of the left ventricle (VCF).1. A reduction of scintigraphic activity was already seen in narrowings of lesser degrees (50%); 2. scintigraphic activity followed the degree of obstruction rather than the contraction abnormality. Perfusion scintigrams are helpful in selecting patients for revascularization.

A case of intramyocardial calcification is presented. The etiology can neither be explained by history, nor by clinical or histological examination. The diagnosis was made by cardiac catheterization and angiocardiography. This showed that the calcification had occurred mostly in the myocardium of the left ventricle and interventricular septum. Because of chronic heart failure surgery was indicated and large amounts of the calcified mass were removed by means of an open heart operation. One and a half years later the patient is much improved though clinical signs of heart failure persist. Possible causes of myocardial calcification are discussed and the problems of surgical intervention outlined.

Hemodynamic studies in pts. with Starr-Edwards disc valves (SE), Lillehei-Kaster valves (LK) and normal mitral valves (N) were performed to compare pressure gradient (deltaP) and volume flow (V). Therefore, synchronous pressure-volume measurements at a diastolic filling time of 500 ms and 250 ms were done. The results show that deltaP in SE valves is much higher than in LK-valves, but this exists only at the beginning of volume acceleration whereas at the end of diastolic time deltaP is similar to that of LK valves. In normal mitral valves initial pressure gradients are also present. Maximum volume flow in SE valves occurs at the end of diastole, but in normal mitral valves and in LK valves, however, it is reached already at the beginning. The studies showed a substantial obstacle to volume flow in SE-disc valves while LK-valves are similar to normal mitral valves.

36 patients with 68 aorto-coronary venous bypass grafts (45 of which were angiographically patent) were examined via DSA (DV12V, serial mode, Philips) and angiography. Imaging was triggered via R waves, and effected in RAO 30 degrees, LAO 60 degrees, and AP projection. 63 of the 68 grafts were correctly detected (92.7%). Two anterior interventricular branch grafts (RIVA = ramus interventricularis anterior) were not visualised via DSA (95.6% sensitivity). One graft each to the RIVA, to the right coronary artery (RCA), and to the posterior branch of the lateral cutaneous branches of intercostal arteries (PLA), were falsely found to be patent (87% specificity). Grafts were visualised in full length. In some cases morphological changes of the walls were also visible.

In 47 patients with proven coronary heart disease a standardized bicycle ergometric test was performed before and after a six-week physical training program, consisting of twice-daily jogging or cycling for 40-min periods. Maximal workload achieved, heart rate, exercise duration and the systolic pressure-rate product were determined at the time of development of limiting symptoms and/or ischaemic ST depression, or when the age-predicted maximum heart rate was reached. Patients were angiographically separated into groups with proximal occlusion of one major coronary vessel and complete collateral filling (group A: LAD 15, LCx or RCA 11) or high-grade (>75–90%, mean: 88.3%) stenosis without collaterals (group B: LAD 9, LCx or RCA 12). In both groups the remaining vessels and post-stenotic wall motion were normal. There were no significant differences in age, sex distribution, site of diseased vessels or ejection fraction. Maximal heart rate and the double product remained unchanged after training in both groups, and did not differ significantly between the two groups. Capacity and duration of exercise significantly increased with training. The frequency of ST segment depression was comparable in both groups. In patients with a positive exercise ECG, the ischaemic threshold, evaluated in terms of the maximal heart rate and the double product, remained constant after training and showed no significant differences between both groups. We thus conclude that under these specific anatomic conditions, collaterals show a significant but limited protective effect during excessive stress, maintained after a short-term training program.

In 173 women less than 50 years of age with myocardial infarction, angiographic evidence of coronary sclerosis was observed in only 108 (62%). Completely normal coronary arteries were found in 15 patients (9%) and in 50 patients (29%) an isolated poorly delineated stenosis was found in the presence of otherwise completely normal coronary arteries. Of the 65 patients with myocardial infarction but without typical coronary sclerosis, 47 (72%) were taking oral contraceptives at the time of infarction. In 60% of the oral contraceptive users with infarction, angiographically, there was no evidence of typical coronary sclerosis. With the exception of cigarette smoking, the number of atherogenic risk factors in these patients was low such that myocardial infarction during treatment with oral contraceptives may possibly represent a separate disease entity distinguishable from coronary sclerosis. In support of this, in some cases, repeat angiography demonstrated spontaneous regression of the isolated stenosis. Etiologically, possible thromboembolic vascular occlusion has been assumed. In women in the premenopausal years, coronary sclerosis is uncommon and usually associated with a substantial number of atherogenic risk factors. In this case, 29% of the women had used oral contraceptives, the causal role of which remains uncertain. Even though oral contraceptive use is associated with a higher risk of myocardial infarction, apparently, it cannot be regarded as a typical atherogenic risk factor.