[An idiopathic floating left-ventricular thrombus]. / Idiopathischer flottierender linksventrikulärer Thrombus.

Four weeks after appendicectomy a 28-year-old man developed dragging pains in the left calf. Left popliteal, posterior tibial and dorsalis pedis arteries could not be palpated. Angiography revealed an embolic occlusion of the left superior femoral artery at the level of the adductor canal. Echocardiography demonstrated a pedunculated left ventricular thrombus, 3.5 x 2.0 cm, as a possible source of the embolus. After successful trifurcation embolectomy and saphenous vein patch-plasty acenocoumarol, 4 mg/d and heparin, 3 x 7500 IU/d were administered. Because the thrombus failed to shrink, systemic thrombolysis, initially 750,000 IU streptokinase and 3000 IU heparin i.v., was begun. After five days the thrombus diameter had decreased to 0.7 cm. But because thrombus movement had increased, streptokinase was replaced by 70 IU/d ancrod i.v. The thrombus completely disappeared within two weeks. The patient was symptom-free during the period of anticoagulation with acenocoumarol. Six months later echocardiography confirmed the absence of thrombus in the left ventricle.

Prevention of perinatal morbidity by tight metabolic control in gestational diabetes mellitus.

In a prospective controlled trial, we studied the effect of tight metabolic control on the outcomes of 102 gestational diabetes mellitus (GDM) pregnancies compared with outcomes of 102 matched nondiabetic control pregnancies. Women with GDM were treated to achieve and maintain a blood glucose concentration of less than 130 mg/dl at 1 h after breakfast. Treatment consisted of a diet low in oligosaccharides and fat and, if necessary, once daily insulin. By the end of gestation, 88 of the 102 women with GDM received insulin at a mean dose of 18 U/day. Duration of insulin therapy ranged from 3 to 32 wk with a median of 11 wk. Perinatal outcome of GDM pregnancies under this management equaled that of control pregnancies. The full spectrum of excess morbidity from GDM was prevented, and normal distribution of birth weight and normal rates of macrosomia, dystrophy, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal acidosis, and low Apgar scores were achieved. No mortality was observed. In addition to the two main study groups, we also studied a third group of 24 women with GDM whose treatment lasted less than or equal to 5 wk due to late diagnosis. This suboptimally treated group demonstrated a significant (P less than .05) increase of macrosomia and umbilical artery acidosis compared with the well-treated GDM group. The study reported herein demonstrates that excess mortality and morbidity typically observed in GDM can be prevented by early institution of tight metabolic control, which required insulin in 86% of our patients.

[Normalization of perinatal morbidity in gestational diabetes by strict metabolic adjustment]. / Normalisierung der perinatalen Morbidität bei Gestationsdiabetes durch straffe Stoffwechseleinstellung.

A prospective study compared the perinatal morbidity of 141 normal pregnancies (group I) with that of 108 pregnancies in whom gestational diabetes had been treated early (group II) and 35 with unsatisfactorily treated gestational diabetes (group III). The therapeutic goal in gestational diabetes was to have a postprandial blood-glucose level of less than 130 mg/100 ml. If this was not achievable through diet alone, insulin was injected once daily. Neonatal macrosomia, dystrophy, acidosis, hyperbilirubinaemia, hypoglycaemia and hypocalcaemia had a normal incidence in group II, but in group III macrosomia was twice as frequent as in group II (P less than 0.02), and acidosis (pH less than 7.20) twice as frequent (P less than 0.05). The results indicate that strict metabolic control in gestational pregnancy will achieve a normal rate of perinatal morbidity.

[Value of lipoprotein electrophoresis for the quantitative assessment of plasma lipoproteins]. / Stellenwert der Lipoproteinelektrophorese für die quantitative Bewertung von Plasmalipoproteinen.

The reliability of semiquantitative densitometric lipoprotein electrophoresis was compared with that of the quantitative determination of plasma lipoproteins by zonal ultracentrifugation on plasma from 73 patients. As an alternative to the measurement of lipoproteins by electrophoresis other, simple laboratory methods were used and also compared with plasma lipoprotein concentrations obtained by zonal ultracentrifugation. It was found that quantitative measurement of plasma lipoproteins by densitometric electrophoresis correlated positively to actual plasma concentration by zonal ultracentrifugation, but other simple methods of lipid determination--of plasma cholesterol; of triglycerides; of HDL and LDL cholesterol--are definitely better for obtaining plasma lipoprotein concentrations. Lipoprotein electrophoresis should not be used for the quantitative determination of plasma lipoproteins.

Stimulating effect of intermediate-density lipoproteins (IDL) from hyperlipemic plasma on hepatic lipase.

The main lipoprotein density classes, namely very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 were investigated with respect to their influence on hepatic lipase (HTGL) activity in vitro. Lipoproteins from pooled normal plasma (NP) and from pooled hyperlipemic plasma (HP) were prepared by means of sequential ultracentrifugation. Hepatic lipase was determined radioenzymatically after preincubation with protamine sulfate. It could be demonstrated that IDL from HP were able to stimulate HTGL activity by approximately 100% above the baseline value. HDL3 from both NP and HP revealed an inhibiting effect on HTGL activity. VLDL, LDL, and HDL2 exhibited no significant effect on HTGL activity. It is speculated that HTGL could possibly represent a second pathophysiological pathway for the catabolism of IDL in hyperlipemia but this presumption is supported by only a few investigations in vivo.

Effect of human plasmalipoproteins on erythropoietic progenitor cells in serum-free cultures.

The purpose of the present study was to investigate the influence of human lipoproteins on CFU-e and BFU-e proliferation from human bone marrow in a serum-free system. In our previously described miniaturized agar system the main lipoprotein-density-classes from human plasma, namely very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL), high density lipoproteins2 (HDL2) and HDL3 and a mixture of all the five lipoproteins were added in rising concentrations (from 1/10 to normal human plasma concentration) to serum-free medium containing delipidated and deionized bovine serum albumin (BSA), iron saturated transferrin and erythropoietin. The results demonstrate that all lipoproteins markedly increased the CFU-e and BFU-e proliferation after 7 and 14 days of incubation, respectively. Moreover, the lipoproteins induced a shift towards a lower threshold concentration of erythropoietin. Serumlike conditions were obtained if LDL and the mixture of lipoproteins were added to serum-free medium. Furthermore, in the serum-free cultures a maturation to the mature erythrocyte could be found.

[Extent of coronary sclerosis in relation to lipoprotein lipase activity and plasma triglyceride levels]. / Ausmass der Koronarsklerose in Beziehung zur Aktivität der Lipoproteinlipase und zur Plasmakonzentration der Triglyceride.

Coronary artery disease (CAD) is closely connected with an increased concentration of cholesterol and a decreased concentration of high-density lipoprotein cholesterol (HDL-chol) in human plasma. No general agreement exists about the atherogenic potential of increased plasma triglycerides. Although both a negative correlation between plasma triglycerides and post heparin lipoprotein lipase (LPL) and a positive correlation between the plasma concentration of HDL-chol and LPL-activity are well documented, only a few studies have investigated the relationship between CAD and LPL. Therefore, 109 male patients with angiographically assessed CAD were investigated with respect to plasma lipids, post heparin LPL, and plasma testosterone and estradiol, which are both known to influence LPL-activity. Many well known results were confirmed. The extent of CAD, assessed by coronary angiography as coronary score (CS), was significantly positively correlated to plasma cholesterol, plasma triglycerides, plasma phospholipids, plasma low-density lipoprotein cholesterol (LDL-chol) and age. CS was significantly negatively correlated to LPL-activity and to the plasma concentration of HDL-chol. LPL itself was significantly negatively correlated to plasma cholesterol, plasma triglycerides and phospholipids, and significantly positively correlated to HDL-chol and plasma testosterone. The most surprising result of this study was the significant correlation between CS and LPL (r = -0.4624; p less than 0.001), a correlation which could explain the increased plasma triglycerides and decreased plasma HDL-chol.

[Autoimmune hemolysis caused by anti-Pr]. / Autoimmunhämolyse durch Anti-Pr.

Following an infection with mycoplasma pneumoniae, an anti-Pr-antibody developed in a hitherto healthy man, aged 41. Within a period of 5 days the antibody caused a severe autoimmune hemolytic reaction. The patient died on the fifth day after admission due to hemolysis and uremia. The autoantibody showed a reactivity with a broad thermal range from 4 degrees C to 37 degrees C. As an initial warning sign, the patient presented an expressed livedo reticularis. Massive wholeblood exchanges could not stop the fatal process.

Essential role of post-heparin lipoprotein lipase activity and of plasma testosterone in coronary artery disease.

89 consecutive men for whom coronary angiography was requested because of suspected coronary artery disease were investigated with respect to plasma lipids, lipoproteins, post-heparin lipoprotein lipase (LPL), and some hormones that influence LPL. The severity of coronary-artery disease was expressed by the coronary score (CS). Coronary-artery disease correlated with total plasma cholesterol, low-density lipoproteins, high-density lipoprotein cholesterol (HDL-chol), and HDL2. In addition, there was a strong negative correlation (r = -0.479, p less than 0.001) between CS and LPL, as well as positive correlations between CS and plasma triglycerides (p less than 0.01) and very low-density lipoproteins (VLDL, p less than 0.01). The impairment of LPL activity correlated with increased VLDL and decreased HDL-chol. The extent of coronary-artery disease is thus strongly influenced by an LPL deficit. LPL activity correlated with plasma testosterone, and there is evidence that low plasma testosterone may be partly responsible for the low LPL and HDL-chol.

[Alcohol-induced type V hyperlipidemia in relation to changes in the chemical composition of HDL2]. / Alkoholinduzierte Typ-V-Hyperlipidämie im Zusammenhang mit Veränderungen der chemischen Zusammensetzung der HDL2.

Alcohol consumption is one of the most common causes of secondary hyperlipidaemia in man, but not all alcohol addicts display hyperlipidaemia. 10 healthy male controls were compared with three groups of patients. The first group consisted of 9 heavy drinkers exhibiting type V hyperlipidaemia under the influence of alcohol. The second group consisted of 7 patients who had displayed type V hyperlipidaemia during alcohol consumption in the past; at the time of investigation, however, they had ceased to drink alcohol at least 6 months previously and were normolipidaemic. The third group consisted of 7 heavy drinkers without hyperlipidaemia. Determinations of plasma lipids and lipoproteins (by means of rate zonal ultracentrifugation), as well as the major apolipoproteins (apo) of high-density lipoproteins2 (HDL2) and HDL3 (by means of polyacrylamide disc-gel electrophoresis) was carried out in all subjects. Two distinct findings were obtained: the one caused by alcohol abuse itself and the other possibly representing a primary trait consisting of an alteration in lipoproteins. In both groups of heavy drinkers the content of apo-CI in HDL2 was lower and the content of apo-AII was higher than in the controls and the abstinent group. In groups I and II with alcohol-dependent type V hyperlipidaemia, the percentage content of total protein in HDL2, as well as the content of apo-D was higher than in controls and in heavy drinkers without hyperlipidaemia. This increased content of apo-D in HDL2 is discussed as being a possible primary marker of alcohol-inducible hyperlipidaemia.

[Lipoproteins, post-heparin lipoprotein lipase and hepatic triglyceride lipase in patients with and without severe hyperlipemia caused by alcoholism]. / Lipoproteine, Post-Heparin-Lipoproteinlipase und hepatische Triglyzeridlipase bei Patienten mit und ohne schwere Hyperlipämie infolge chronischem Alkoholismus.

Because of the high incidence for development of a secondary hyperlipemia during chronic alcohol intake, this study was performed to look for a possible reason, why some patients produce severe hyperlipemia and other ones not. 15 male patients with chronic alcoholism (group I) who produce under influence of alcohol a secondary type-V hyperlipoproteinemia (type-V HLP) were compared with 15 male controls. Additionally, 8 male patients with chronic alcoholism (group II) who were normolipemic under alcohol abuse, and 7 male patients (group II) who had also produced type-V HLP under chronic alcohol abuse, but were teetotal since at least 6 months, were investigated. In comparison with controls, patients of group I showed significantly (p less than 0.01) increased plasma concentrations of very low-density lipoproteins (VLDL) and significantly decreased plasma concentrations of low-density lipoproteins (LDL), high-density lipoproteins2 (HDL2) and HDL3 (all p less than 0.01). Furthermore, the activities of postheparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) were significantly decreased (both p less than 0.01). In patients of group III, the plasma concentrations of lipoproteins did not differ significantly from controls, but the activity of LPL was also significantly impaired (p less than 0.01), whereas the activity of HTGL was distinctly (p less than 0.01) increased. No significant difference between patients of group II and controls could be demonstrated. It is concluded that severe alcohol intake strongly impairs LPL in patients with chronic alcoholism. The pronounced increase of HTGL in patients of group III seems to protect these individuals from producing severe hyperlipemia under the influence of alcohol.

[Distinct increase of plasma concentrations of high-density lipoprotein 2 and post-heparin lipolytic activity by constant moderate alcohol intake]. / Deutliche Erhöhung der Plasmakonzentration der HDL2 und der postheparin-lipolytischen Aktivität durch konstanten mässigen Alkoholkonsum.

In a 69-year-old man with familial hypercholesterolemia, markedly increased plasma concentrations of high-density HDL2 lipoprotein (HDL2) were found. The patient showed no signs of atherosclerotic macro- nor microangiopathy. As a possible reason for the increase of HDL2 a daily intake of 3/8 litre red wine was assumed. On three days (day 1, day 21, day 42) the influence of alcohol on the major lipoprotein density classes (i.e. very low-density lipoproteins [VLDL], intermediate-density lipoproteins [IDL], low-density lipoproteins [LDL], HDL2 and HDL3, all by means of rate zonal ultracentrifugation) and on postheparin lipolytic activity (PHLA) was investigated. At day 1 the patient was under the influence of the usual daily alcohol intake. From day 1 till day 21 patient drank no alcoholic beverages. From day 21 till day 42 the patient returned to his daily intake of 3/8 litre red wine. During the sober phase the plasma concentration of HDL2 decreased to approximately one quarter of the plasma concentration at day 1. Additionally, PHLA decreased markedly. During the daily alcohol consumption till day 42, the plasma concentration of HDL2 again rose approximately to the value of day 1 and PHLA distinctly increased. It is concluded that moderate alcohol consumption may increase the plasma concentration of the antiatherogenic HDL2 in some patients. This patient with familial hypercholesterolemia appears to be protected from premature atherosclerotic complications by his pronounced increase in plasma concentration of HDL2.

Post-heparin lipolytic activities and alterations of the chemical composition of high density lipoproteins in alcohol-induced type V hyperlipidemia.

In order to study the effects of chronic alcoholism, 3 groups of patients were investigated and compared to 10 healthy controls. Group I consisted of 9 heavy drinkers, who exhibited type V hyperlipidemia (HLP) under alcohol intake. Group II consisted of 7 patients, who previously had type V HLP under the influence of alcohol. At the time of the investigation, however, they had ceased alcohol drinking for at least 6 months and were normolipidemic. Group III consisted of 7 heavy drinkers without hyperlipidemia. Compared to controls, group I had significantly decreased plasma concentrations of high density lipoproteins2 (HDL2) and HDL3 (both P less than 0.01); activities of post-heparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) as well were excessively decreased (both P less than 0.01). In group III LPL was also decreased (P less than 0.01), but HTGL was distinctly (P less than 0.01) higher than in controls. No such differences could be demonstrated for the patients of group II. Acute alcohol withdrawal from a patient suffering from alcoholism with HLP led to a sharp increase of LPL with a simultaneous decrease of VLDL within 2 days and a more delayed increase of LDL, HDL2 and HTGL, all reaching normal values within 12 days after cessation of alcohol drinking. With respect to the apolipoprotein (apo) composition of HDL2, patients of group I and group III exhibited a significantly lower percentual content of apo C-I at the expense of a significantly higher content of apo A-II as compared to controls and patients of group II. In group I and II, the percentual content of apo D in HDL2 was significantly higher than in controls and in group III. It is concluded that severe alcohol intake strongly impairs LPL in patients with HLP. The pronounced increase of HTGL in some patients (group III) may protect these individuals from HLP. The increased content of apo D in HDL2 may be a possible primary trait for alcohol-inducible HLP.

[Reduction of post-heparin lipoprotein lipase activity by acidotic blood pH]. / Aktivitätsverminderung der post-Heparin-Lipoproteinlipase bei azidotischem Blut-pH.

Diseases associated with acidotic blood-pH, such as chronic renal disease, diabetes mellitus or chronic alcoholism, show a marked impairment of lipoprotein lipase. Therefore we influenced blood-pH in 3 healthy subjects by infusions to get alkalotic, neutral and acidotic blood-pH on three days in series. On each day blood-pH from capillary blood and post-heparin lipoprotein lipase from fasting plasma was determined. In comparison to neutral blood-pH in vivo, alkalosis did not influence lipoprotein lipase. In contrast, during artificial acidosis, lipoprotein lipase was impaired significantly (p less than 0.01). Therefore, it seems, that acidosis inhibits lipoprotein lipase in vivo.

[Atherosclerosis in familial hypercholesteremia possibly induced by defective HDL]. / Atherosklerose bei familiärer Hypercholesterinämie möglicherweise durch fehlerhafte HDL bedingt.

The distinct increase in the highly atherogenic plasma low-density lipoproteins (LDL) caused by the wellknown LDL-receptor defect is considered to be responsible for the development of atherosclerosis in familial hypercholesterolemia (FH). In contrast to the atherogenic LDL, the high-density lipoproteins (HDL) are considered to have a protective effect against the development of atherosclerosis and have hitherto been insufficiently investigated in association with FH. HDL2 are assumed to be important in the removal of free cholesterol from the peripheral tissue to the liver, but this hypothesis needs to be supported by further experimental investigations. In this study 18 patients (7 men/11 women) with familial hypercholesterolemia (FH) were compared with 18 healthy controls (8 men/10 women). From fasting plasma the following parameters were determined: cholesterol, triglycerides, phospholipids, HDL-cholesterol, by rate zonal ultracentrifugation the lipoproteins VLDL (very low-density lipoproteins), IDL (intermediate-density lipoproteins), LDL (low-density lipoproteins), HDL2 and HDL3, as well as the activities of lipoprotein lipase (LPL) and hepatic lipase (HTGL). In addition, the percentage composition of the major apolipoproteins (apo) of HDL2 and HDL3 were determined by polyacrylamide disc-gel electrophoresis. In LDL of patients with FH the percentage amount of protein was significantly (p less than 0.01) smaller than in controls. Furthermore, in HDL2 of patients with FH, the percentage content of apo-A II and apo-D was significantly (both p less than 0.01) higher than in controls. In HDL3 of patients with FH a significantly smaller (p less than 0.02) amount of apo-E was revealed than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoproteins, HDL-apolipoproteins, activities of hepatic lipase and lecithin-cholesterol acyltransferase in the plasma of patients with post-alcoholic end-stage liver cirrhosis.

12 patients with unequivocal post-alcoholic end-stage liver cirrhosis were compared with 12 healthy controls with regard to the plasma concentrations of lipids, lipoproteins (by rate zonal ultra-centrifugation) and apolipoproteins of high-density-lipoproteins (HDL) (by disc electrophoresis), as well as to the activities of lecithin-cholesterol acyltransferase (LCAT) in plasma and of hepatic lipase (HL) in post-heparin plasma. The cirrhotic group showed the following differences (all significant at the p less than 0.01 level) from the control group: Total cholesterol, HDL-cholesterol, very-low-density-lipoproteins (VLDL), HDL, and HL were decreased. Intermediate-density-lipoproteins (IDL) were not detectable in the cirrhotic group. Low-density-lipoproteins (LDL) did not differ significantly from controls. However, LDL from cirrhotic patients contained more triglycerides but less esterified and free cholesterol (all p less than 0.01). The percentage apolipoprotein composition of HDL did not differ significantly between controls and cirrhotics. Surprisingly, LCAT activity in plasma as well as the ratios between esterified and free cholesterol in plasma, LDL, and HDL were nearly identical in both groups. It seems likely that LCAT activity decreases only in the states of acute or subacute liver injury or of biliary obstruction. Severe chronic liver injury or of biliary obstruction. Severe chronic liver damage as in our cases of end-stage liver cirrhosis without any signs of acute liver injury exhibits apparently no defect in cholesterol esterification.

[Livedo reticularis: dermatologic alarm signal in cold agglutinin disease]. / Livedo reticularis: Dermatologisches Alarmzeichen bei Kälteagglutininkrankheit.

A hitherto healthy adult man developed paroxysmal cold agglutinin disease following an infection of the upper respiratory tract with mycoplasma pneumoniae. Despite continuous blood exchange he died of massive intravascular hemolysis and uremia after 5 days. A presenting striking symptom of this rapidly fatal disease was the acute onset of generalized livedo reticularis. The disease was caused by the rare anti Pr-cold agglutinins which are capable of eliciting hemolysis even in low titers and, in the present case, at body temperature.