Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii.

A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by ß-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.

Platelet function analyzer (PFA-100) as a useful tool for the prediction of transfusion requirements during aortic valve replacement.

BACKGROUND: Shear stress-induced hemostatic abnormalities, particularly loss of the hemostatically most competent, highest molecular weight von Willebrand factor multimers, are common in patients with aortic valve stenosis. Although controversially discussed, these hemostatic defects might be associated with an increased risk of bleeding during aortic valve replacement. Since the determination of closure times with a platelet function analyzer is sensitive for the detection of defects of primary hemostasis including shear stress-induced von Willebrand factor abnormalities, this study was performed to evaluate a method to predict intraoperative transfusion requirements in this setting. METHODS: Fifty patients (mean age ± SD: 68 ± 9 years, range 40-85 years) admitted for aortic valve replacement were enrolled in the study. Closure times of epinephrine/collagen and ADP/collagen cartridges were determined with a platelet function analyzer in the absence of antiplatelet agents. Results were compared to those obtained in healthy individuals without medication. The probability that a patient would require a transfusion of packed red cells (RBC) and fresh frozen plasma (FFP) was calculated for each obtained closure time using a multiple regression model. RESULTS: Compared to controls, patients undergoing aortic valve replacement had a significantly higher incidence of prolonged closure in the platelet function analyzer. The prolonged closure time of both epinephrine/collagen and ADP/collagen cartridges was significantly correlated with intraoperative transfusion of RBC, but not FFP. CONCLUSIONS: In patients undergoing aortic valve replacement, prolongation of closure times as determined by a platelet function analyzer is frequently observed, indicating the presence of shear stress-induced defects of primary hemostasis. Since the prolongation of closure times is significantly correlated to the probability of intraoperative transfusion, this method might offer a significant contribution to the preoperative risk stratification of patients.

Platelet-function analyzer closure times indicate shear stress-induced hemostatic abnormalities in patients with aortic valve stenosis and correlate with perioperative transfusion requirements.

BACKGROUND: Shear stress-induced hemostatic abnormalities are highly prevalent in patients with aortic valve stenosis. In this study, we determined closure times with a platelet-function analyzer (PFA-100, Dade Behring, Marburg, Germany) in patients admitted for aortic valve replacement to assess the correlation with the severity of aortic valve stenosis, blood loss, perioperative transfusion requirements, and need for re-thoracotomy. PATIENTS AND METHODS: Fifty consecutive patients (mean age [+/- SD] 68 +/- 9 years) were enrolled. Closure times of epinephrin/collagen and adenosine diphosphate (ADP)/collagen cartridges were determined at least ten days after discontinuation of antiplatelet medication and compared to those of healthy control subjects without medication. RESULTS: Closure times of epinephrin/collagen (210 +/- 69 sec vs. 140 +/- 50 sec, p < 0.0001) and ADP/collagen (145 +/- 58 sec vs. 108 +/- 45 sec, p < 0.0001) cartridges were prolonged in patients with aortic valve stenosis. Intraoperative transfusion of red blood cell units was associated with the closure times of epinephrin/collagen (r = 0.28, p = 0.04) and ADP/ collagen cartridges (r = 0.28, p = 0.04). Total transfusion of red blood cell units was associated with ADP/ collagen closure times (r = 0.31, p = 0.02), but not epinephrin/collagen closure times (r = 0.26, p = 0.07). No significant association of closure times with intraoperative, postoperative and total transfusion of fresh frozen plasma units was observed. CONCLUSIONS: Prolongation of closure times determined with a platelet-function analyzer is highly prevalent in patients with aortic valve stenosis and appears to reflect shear stress-induced hemostatic abnormalities. Since prolonged closure times are associated with increased perioperative transfusion of red blood cell units, the assay could significantly contribute to the identification of individuals at risk.

[Thromboembolic risk and prophylaxis in hospitalized surgical and internal medicine patients. German results of the international ENDORSE study]. / Thromboembolierisiko und -prophylaxe internistischer und chirurgischer Patienten im Krankenhaus. Deutsche Ergebnisse der internationalen ENDORSE-Studie (ENDORSE Deutschland).

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) leads to an increased morbidity in hospitalized patients. This multinational cross-sectional survey was designed to assess the prevalence of VTE risk factors and to determine the proportion of at-risk patients who receive effective VTE-prophylaxis. The results of the 16 participating German hospitals of the study are presented and compared with the international results. PATIENTS AND METHODS: All hospital inpatients aged >or= 40 years admitted to a medical ward and all surgical inpatients aged >or= 18 years were enrolled. The American College of Chest Physicians (ACCP) guidelines (2004) were applied to assess VTE risk and to determine whether patients were receiving recommended VTE prophylaxis. RESULTS: Overall, 2,370 patients were enrolled: 1,210 (51 %) were categorised as surgical and 1,160 (49 %) as acute medically ill. 838 (69 %) of surgical and 479 (41 %) of medical patients were judged to be at risk for VTE. Of the surgical patients at risk, 772 (92 %) received ACCP-recommended VTE prophylaxis, compared with 337 (70 %) medical patients at risk of VTE. Low-molecular weight heparins were most frequently used. CONCLUSIONS: In total, in comparison to other countries, Germany has a leading position in the implementation of international guidelines with regard to VTE prophylaxis. Whereas in a surgical ward effective VTE prophylaxis is consistently standard care, in the medical indications there is still room for improvement in terms of stratification of VTE risk and corresponding VTE-prophylaxis.

Platelet receptor HPA-1 polymorphism of alphaIIbbeta3 and 807 C/T polymorphism of alpha2beta1 and Buerger's disease.

Thromboangiitis obliterans or Buerger's disease is an episodic and segmental inflammatory and thrombotic process of the medium and small arteries of the lower extremities. Even though the disease was described 90 years ago, the etiopathogenesis is still under consideration. Afflicted patients are mostly young male cigarette smokers without signs of atherosclerosis or other risk factors for peripheral arterial occlusive disease. This indicates that hereditary thrombophilic factors could play a role in the etiopathogenesis. Recently, increasing evidence shows that platelet receptor polymorphisms (HPA-1 polymorphism of beta3 subunit of alphaIIbbeta3 and 807 C/T polymorphism alpha2beta1) are associated with early onset of arterial thrombosis (myocardial infarction, stroke). This case-control study was designed to assess whether the 807 C/T polymorphism or the HPA-1 polymorphism is involved in the pathogenesis of Buerger's disease or has any influence on the clinical course of Buerger's disease. Eighteen patients with Buerger's disease and 81 (sex and age matched) healthy control subjects (mean age 44 +/- 10 vs 45 +/- 8 years, respectively) were genotyped for platelet receptor HPA-1 and GPIa 807 C/T polymorphism. The gene frequency of HPA-1 and GPIa 807 C/T polymorphisms was identical in both groups. Prevalence of hetero- and homozygous carriers of the HPA-1b allel (1a1b and 1b1b genotype) as well as the prevalence of the 807 C/T and 807 T/T carriers did not differ significantly between the two groups, p >0.05. The grade of clinical disease manifestation as well as disease progression did not reveal any significant relationship with HPA-1 and 807 C/T polymorphisms. A relationship between the age at onset of the disease and HPA-1 polymorphism was not found. Otherwise analysis of the GPIa 807 C/T platelet receptor polymorphism showed that the average age of patients who are carriers of the T allele at early onset of disease was 32 +/- 6 years (range 27-48 years) compared to 42 +/- 6 years (range 34-53 years) of the C/C carriers (p <0.05). This indicates that the GPIa 807 C/T polymorphism does not represent a risk factor for Buerger's disease itself, but could be associated with premature onset of this disorder in predisposed individuals.

[Pregnancy-associated venous thromboembolic disease: prediction, prevention, and therapy]. / Venöse Thrombose in der Schwangerschaft. Prädiktion, Prävention und Therapie.

Thromboembolic disease remains a leading cause of maternal mortality during pregnancy and the puerperium. Rational and risk-adapted administration of heparin prophylaxis depends on 1. the identification of those women who have an increased risk of thrombosis and 2. the accurate quantification of this risk. In women without prior thrombosis, the presence of a heterozygous factor V Leiden or heterozygous G20210A mutation in the prothrombin gene is associated with a pregnancy-associated thrombotic risk of approximately 1 in 400. Thus, in pregnant carriers of either one of these mutations the risk of venous thromboembolism is low. Therefore, no heparin prophylaxis is recommended. A combination of the two genetic risk factors can increase the risk to a modest level of 1 in 25. In women with a single episode of prior thrombosis associated with a transient risk factor, e.g. surgery or trauma, and no additional genetic risk factor, the probability of a pregnancy-associated thrombosis appears also to be low. However, data are sparse and conflicting. In contrast, in women with a prior idiopathic venous thrombosis who carry an additional hereditary risk factor or who have a positive family history of thrombosis, a high risk (>10%) can be expected supporting the indication for active antepartum and postpartum heparin prophylaxis. Despite the remarkable progress in risk stratification, the absolute magnitude of risk and the optimal management in many cases is an issue of ongoing debate.

Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction.

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.

[Anticoagulation as an oncological therapy principle]. / Antikoagulation als onkologisches Therapieprinzip.

The association of cancer with thromboembolic events has been established for more than hundred years. While the thrombophilic diathesis of tumor patients and the neoplastic thrombogenesis have been elucidated pathophysiologically, at least in part, there is growing experimental and clinical evidence that factors of plasmic hemostasis promote tumor growth, angiogenesis, and metastasis. Thus, the rationale for antithrombotic prophylaxis and therapy of tumor patients might not only be based on the prevention of thromboembolic complications but also on the potentially antineoplastic and antimetastatic effects of pharmacological anticoagulation. Encouraging results of clinical studies indicate that prophylactic and therapeutic anticoagulation might improve the survival of selected patients with cancer.

Methylenetetrahydrofolate reductase gene polymorphism and glucocorticoid intake in children with ALL and aseptic osteonecrosis.

BACKGROUND: Methotrexate is an essential part of the treatment of acute lymphoblastic leukaemia (ALL). Due to an increased survival of ALL patients, complications like BME (bone marrow edema) and AON (aseptic osteonecrosis) have become a matter of increasing importance. The aim of the study was to find out if a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene predisposes to the development of BME and/or AON. Furthermore the cumulative prednisone equivalent dose per kilogram body weight was compared in a matched-pairs analysis. PATIENTS AND METHODS: A retrospective analysis of the MTHFR polymorphism of 87 patients was performed (48 male, 43 female). 14/87 patients were diagnosed with BME and/or AON (16 %). RESULTS: 42/73 patients without BME and/or AON (43 male, 34 female, median age 5.3 yrs) and 10/14 patients with BME/AON (5 male, 9 female, median age 10.2 years) presented with a MTHFR-polymorphism (p = 0.28). 14,3 % of the patients with MTHFR-polymorphism but without BME and/or AON (6/42) and 70 % of the patients with MTHFR-polymorphism and with BME and/or AON (7/10) were over 10 years of age at ALL diagnosis (p = 0.002). The mean cumulative prednisone equivalent dose per kilogram body weight was 98.0 mg, compared with 100.0 mg in the matched pairs group. CONCLUSIONS: The age of the patients at diagnosis seems to be a risk factor for the development of BME and/or AON as also seen in previous studies. If MTHFR polymorphism is an additional risk factor it was not borne out by this study, possible due to the small number of patients analyzed. This aspect is worth to be proven with a large group of patients considering the MTX pharmacokinetic and leucovorine rescue.

[Safety and efficacy of LK565--a new polymer ultrasound contrast medium]. / Untersuchungen zur Sicherheit und Effizienz von LK565--einem neuen Polymer-Ultraschallkontrastmittel.

We tested a newly developed ultrasound contrast agent (LK565) from poly-aspartic acid (PAA; particle size 3 microns; particle content: air) in 15 healthy male probands (20-38 years) in doses of 10, 30 and 100 mg intravenously. One day and immediately before the study a routine laboratory test, an ECG and an EEG were performed. The EEG was continued through the complete time period that the ultrasound contrast lasted, i.e., up to one hour after the injection. All probands were followed clinically for 24 hours when the routine laboratory and the ECG were repeated. All subjects tolerated the contrast agent well. There were no changes in either the EEG or in the ECGs performed throughout the study. There were no significant laboratory changes except for a small and transient increase in the neutrophil count in five probands receiving the highest dose. All injections with 10 mg led to a significant improvement in the color Doppler signal. All injections with 30 and 100 mg led to a very strong echo contrast lasting for 5 to 12 minutes in the harmonic B-mode. Using the latter, fragments of intramyocardial coronaries could be visualized. The tested ultrasound polymer contrast agent was safe, well tolerated and efficient in this acute study.

Rationale and design of the LURIC study--a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease.

BACKGROUND AND AIM: Coronary artery disease (CAD), arterial hypertension and Type 2 diabetes mellitus are common polygenetic disorders which have a major impact on public health. Disease prevalence and progression to cardiovascular complications, such as myocardial infarction (MI), stroke or heart failure, are the product of environment and gene interaction. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study aims to provide a well-defined resource for the study of environmental and genetic risk factors, and their interactions, and the study of functional relationships between gene variation and biochemical phenotype (functional genomics) or response to medication (pharmacogenomics). Long-term follow-up on clinical events will allow us to study the prognostic importance of common genetic variants (polymorphisms) and plasma biomarkers. SETTING: Cardiology unit in tertiary care medical centre in south-west Germany. STUDY DESIGN: Prospective cohort study of individuals with and without cardiovascular disease at baseline. PATIENTS AND METHODS: LURIC is an ongoing prospective study of currently > 3300 individuals in whom the cardiovascular and metabolic phenotypes CAD, MI, dyslipidaemia, hypertension, metabolic syndrome and diabetes mellitus have been defined or ruled out using standardised methodologies in all study participants. Inclusion criteria for LURIC were: German ancestry (limitation of genetic heterogeneity) clinical stability (except for acute coronary syndromes [ACSs]) availability of a coronary angiogram (this inclusion criterium was waived for family members provided that they met all other inclusion and exclusion criteria) Exclusion criteria were: any acute illness other than ACSs any chronic disease where non-cardiac disease predominated a history of malignancy within the past five years. Exclusion criteria were pre-specified in order to minimise the impact of concomitant non-cardiovascular disease on intermediate biochemical phenotypes or on clinical prognosis (limitation of clinical heterogeneity). A standardised personal and family history questionnaire and an extensive laboratory work-up (including glucose tolerance testing in non-diabetics and objective assessment of smoking exposure by determination of cotinine plasma levels) was obtained from all individuals after informed consent. A total of 115 ml of fasting venous blood was sampled for the determination of a pre-specified wide range of intermediate biochemical phenotypes in serum, plasma or whole blood, for leukocyte DNA extraction and immortalisation of B-lymphocytes. Biochemical phenotypes measured included markers of endothelial dysfunction, inflammation, oxidative status, coagulation, lipid metabolism and flow cytometric surface receptor expression of lympho-, mono- and thrombocytes. In addition, multiple aliquots of blood samples were stored for future analyses. RESULTS: A total of 3500 LURIC baseline measurements were performed in 3316 individuals between July 1997 and January 2000. The baseline examination was repeated within a median of 35 days in 5% of study participants (n = 166, including a third examination in 18 after a median of 69 days) for pharmacogenomic assessment of lipid-lowering therapy and for quality control purposes. A five-year follow-up on major clinical events (death, any cardiovascular event including MI, stroke and revascularisation, malignancy and any hospitalisation) is ongoing. The clinical phenotypes prevalent at baseline in the cohort of 2309 men (70%) with a mean age of 62 +/- 11 years and 1007 women (30%), mean age 65 +/- 10 years, were angiographically-documented CAD in 2567 (79%), MI in 1368 (41%), dyslipidaemia in 2050 (62%) with hypercholesterolaemia > or = 240 mg/dl (27%), hypertriglyceridaemia > or = 150 mg/dl (44%) and HDL-cholesterol < or = 35 mg/dl (38%) in individuals not treated with lipid-lowering agents, systemic hypertension in 1921 (58%), metabolic syndrome in 1591 (48%), Type 2 diabetes in 1063 (32%) and obesity defined by body mass index > or = 30 kg/m2 in 770 (23%). Control patients in whom CAD had been ruled out angiographically were five years younger than those with CAD (59 +/- 12 and 64 +/- 10 years, respectively; p < 0.001), twice as often females (48% compared to 25% females in the CAD group, p < 0.001) and had significantly less cardiovascular risk factors than individuals with CAD. The prevalence of specific cardiovascular risk subsets in LURIC, such as the elderly (> or = 75 years), was 375 (11%), while 213 (6%) were young adults (< 45 years) and 904 (27%) were postmenopausal women (90% of all females). A low risk status (< or = 1 out of the four traditional risk factors: dyslipidaemia, smoking, hypertension and diabetes mellitus) was identified in 314 (9%) individuals of the entire cohort (5% in CAD and 26% in controls, p < 0.001) and 97 (3%) carried none of the four risk factors (1% in CAD and 9% in controls, p < 0.001). (ABSTRACT TRUNCATED)

Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, myocardial infarction, and death.

Recently, we have demonstrated that human platelet antigen 1b (HPA-1b or P1A2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-lb does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-lb on the outcome in patients after coronary-artery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronary-artery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-lb was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA-1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-lb had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Liver function in patients with pulmonary emphysema due to severe alpha-1-antitrypsin deficiency (Pi ZZ).

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Transthoracic and transesophageal echocardiography to diagnose ventricular septal rupture: importance of right heart infarction.

BACKGROUND: Rapid and accurate diagnosis of ventricular septal rupture (VSR) remains difficult, and the monitoring of hemodynamic deterioration is a prerequisite for the institution of adequate therapy. The timing of surgical repair is a matter of controversy. METHODS: Transthoracic, transesophageal, color Doppler, and contrast echocardiography were evaluated in 17 patients with VSR in whom the diagnosis was confirmed by catheterization, surgery, or necropsy. RESULTS: Routine transthoracic echocardiography visualized VSR in four out of 17 patients and, with additional views, in 12 out of 17 patients. Color Doppler echocardiography identified the rupture in 15 out of 16, and contrast echocardiography in 11 out of 11 patients. VSR was identified using transesophageal echocardiography in six out of nine patients, and using color Doppler and contrast echocardiography in all patients. Eight out of 10 patients who developed right heart myocardial infarction (RMI) died, whereas all patients without RMI survived (P = 0.0070). Similarly, eight out of 10 patients with shock died, whereas all patients without survived (P = 0.0070). Shock occurred more often in patients with RMI (eight out of 10) than in patients without (two out of six). All patients with both RMI and shock died, whereas those without both conditions survived (P = 0.0002). CONCLUSION: Modern echocardiography is the method of choice in the diagnosis of VSR. Right ventricular function should be evaluated in patients with VSR because patients with RMI are at high risk of hemodynamic deterioration, with poor outcome. RMI, visible as abnormal wall motion, was identified better with transesophageal than with transthoracic echocardiography.

Diagnosis of papillary muscle rupture after acute myocardial infarction by transthoracic and transesophageal echocardiography.

The sensitivity of transthoracic echocardiography to visualize the structural abnormality of papillary muscle rupture (PMR) after acute myocardial infarction can be anticipated to average about 50%; therefore, we evaluated five patients exhibiting the condition with both transthoracic and transesophageal echocardiography. The use of the two imaging techniques resulted in the fact that no instance of PMR was missed. Using transthoracic echocardiography in two patients and transesophageal echocardiography in four, the ruptured papillary muscle was visualized directly. Mitral insufficiency as an indirect sign was observed in all patients. In one patient the papillary muscle rupture developed in a mitral valve previously affected by endocarditis. All patients underwent mitral valve replacement and coronary artery bypass grafting. The diagnosis was confirmed at surgery in all patients. Four patients died in hospital, the fifth 5 months later. We recommended that transesophageal echocardiography be performed in patients with suspected PMR if transthoracic echocardiography does not provide an unequivocal diagnosis.

[Diastolic flow analysis of the left ventricle after myocardial infarct]. / Diastolische Flussanalyse des linken Ventrikels nach Myokardinfarkt.

The diastolic function of the left ventricle was investigated in 12 normal young volunteers, 10 older volunteers, 10 patients without evidence of coronary artery disease, 26 patients with inferior wall and 19 patients with anterior wall infarction at eight locations of the total circumference of the left ventricle using pulsed wave Doppler. The ratio of early diastolic inflow (Vmax E) to the maximal velocity of atrial contraction (Vmax A) was determined. Furthermore, the delay between the end of electrical diastole until the end of the A-wave of the pulsed Doppler was measured. The results were compared with a clinically used marker of myocardial ischemia, treadmill exercise testing. The E/A ratio was 2.03 +/- 0.51 in normal volunteers, 1.16 +/- 0.41 in older volunteers, 1.41 +/- 0.59 in patients without evidence for coronary artery disease, 1.28 +/- 1.13 in patients with inferior and 1.08 +/- 0.41 in patients with anterior wall infarction (p = 0.020 ANOVA). The diastolic delay at the apex was 47.3 +/- 8.9 ms in normal volunteers, 78.3 +/- 8.3 ms in older volunteers, 79.1 +/- 13.7 ms in patients without coronary artery disease, 109.1 +/- 12 ms in patients with inferior and 169.5 +/- 18.8 ms in patients with anterior wall infarction (p = 0.000 ANOVA). There was a correlation between the latter parameter of delay and the amount of pathological wall segments at wall motion analysis (r = 0.61, p = 0.007). In two patients with anterior myocardial infarction (11%) with significant diastolic delay intraventricular thrombi developed consecutively.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of rapid versus prolonged healing of infective endocarditis by monitoring vegetation size.

The diagnostic value of transesophageal echocardiography in monitoring the clinical course has been evaluated in 83 patients with echocardiographic evidence of infective endocarditis. A total of 103 vegetations attached to the aortic or mitral valves were detected by use of the transesophageal approach. The patients were monitored for a mean of 74 weeks and underwent a minimum of two consecutive transesophageal echocardiographic examinations. Group A included patients with increasing or remaining constant size of vegetation (8.2 +/- 1.5 to 11.2 mm, p less than 0.05) during 4 to 8 weeks of antimicrobial therapy, whereas group B was formed by patients with decreasing vegetation size (8.3 +/- 0.8 to 4.9 +/- 0.8 mm, p less than 0.05). The incidences of complications after diagnosis and onset of therapy was higher in group A than in group B: valve replacement (45% versus 2%, p less than 0.05), embolic events (45% versus 17%, p less than 0.05), perivalvular abscess formation (13% versus 2%, p less than 0.05), and mortality (10% versus 0%, respectively, p less than 0.05). Staphylococcus aureus was the most frequent organism isolated in group A (44% versus 11% in B, p less than 0.05) and Streptococcus viridans in group B (33% versus 18% in A, p less than 0.05). Blood cultures were negative in nearly 50% of the patients in each group. There was no difference in the incidences of complications in patients with positive or negative blood cultures. We conclude that an increase in vegetation size during antibiotic therapy predicts a prolonged healing phase of infective endocarditis. This prolonged healing period is associated with a significantly increased risk of complications, independent of blood culture results. Monitoring vegetation size contributes important information concerning prognosis and stage of risk, and it aids in the choice of patient management in infective endocarditis. Because embolic events after diagnosis and onset of treatment are less frequent in rapid-healing endocarditis, surgery cannot be recommended to prevent further events taking into account the high risk of surgery.

New mechanical devices for treatment of coronary artery disease.

Percutaneous high-speed coronary rotablation allows to remove arterio-sclerotic material from the vessel wall. A diamond-coated (15-30 microns) brass burr drill fastened to a flexible drive shaft rotating and tracking along a drill coaxial guide wire is used. The turbine rotates the drive shaft at 150,000-190,000 rpm. High-frequency rotational angioplasty was successful in 27 of 28 patients, but in about 34% additional PTCA was necessary. Only one patient went to bypass surgery, and myocardial infarction (CK less than 150 u/l) occurred in only one of 28 patients. No vessel perforation was observed. All vessels were open at 24 h control. The restenosis rate was not increased. The main indication for high-speed rotational angioplasty seems to be rigid sclerotic lesions that cannot be passed by a conventional balloon catheter. Whether restenosis rate can be reduced by this method will be judged in future studies. In order to avoid acute complications of PTCA and to reduce restenosis rate, coronary stents were developed. Self-expandable and balloon-expandable stents are available. It could be demonstrated that these stents can be used as a bail-out system and can block elastic recoil of coronary arteries. The major remaining problem is that of subacute closure of coronary vessels. In order to prevent this, treatment with coumarine, acetylsalicylic acid, and dipyridamol is necessary. Coronary stents can be successfully delivered in more than 90% of the patients, as demonstrated by a cooperative study. In a highly selective patient group using single stents, restenosis rate measured 15%, but was higher in patients with multiple stents.