Contribution of each ventricular wall to ventricular interdependence

Summary The influences of presure and volume changes in one ventricle on the other ventricle may be determined from the relative compliances of the ventricular free walls and the interventricular septum. If this is correct, then disease states which alter regional compliances should influence the diastolic mechanical coupling between the ventricles. To examine this hypothesis, the hearts of 15 canine dogs were removed and placed in cool cardioplegic solution. Balloons were inserted into each ventricle and the right and left ventricular pressure (P_r, P_l) and volume (V_r, V_l) changes caused by changing the pressure and volume of the other ventricle were recorded. Acute changes in right ventricular free wall (N=5), septal (N=5), and left ventricular free wall (N=5) compliances were induced by glutaraldehyde injections. After injecting glutaraldehyde into the right coronary artery, P_l/V_r, V_l/V_r, P_r/P_l, and P_r/V_l increased significantly (P<0.05). After septal artery injection, pressure and volume transfer between the ventricles was significantly depressed. After left coronary artery injection, P_l/P_r, P_l/V_r, P_r/V_l, and V_r/V_l increased significantly (P<0.05). Thus, selective alterations in the mechanical coupling between the ventricles occurred following changes in right ventricular, septal, and left ventricular free wall compliances. Such changes may be important in diseases which primarily affect one side of the heart.This study was supported in part by NIH Grant No. HL 36068 by a grant from the American Heart Association, New Jersey Chapter.     

Über Beziehungen zwischen Steroiden und krebserzeugenden Verbindungen (V.)

Zusammenfassung Suspensionen von 2-acetamino-^1.3.5(10)-oestratrien und 3-Acetamino-^1.3.5(10)-oestratrien in Tricaprylin und solche in Glycerin wurden Mäusen subcutan injiziert. Tumoren an der Applikationsstelle wurden nicht beobachtet, doch wurde eine gegenüber den Kontrollen vermehrte Bildung von Tumoren entfernt vom Applikationsort beobachtet.—Unwirksam erwies sich 3-Amino-^1.3.5(10)-oestratrienol-(17) im Pinselungstest an der Maus; im Fütterungstest nach Huggins an der weiblichen Sprague-Dawley-Ratte entstand bei 1 von 10 Tieren ein Mammacarcinom. Die bisher erzielten Ergebnisse sollten dazu anregen, Vertreter dieser Verbindungsklasse auf breiterer Basis zu prüfen.—Eine hypothetische Reaktionsfolge für die Umwandlung von natürlichen Oestrogenen über ihre p-Chinole in die Amino-Analoge (Transaminierung mit Pyridoxamin-5-phosphat) wird diskutiert.

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Relations between steroids and carcinogenic compounds (V.)2-Acetamino- and 3-Acetamino-^1.3.5(10)-estratriene and 3-Amino-^1.3.5(10)-estratrienol-(17)

Summary Suspensions of 2-acetamino-^1.3.5(10);-estratriene and 3-acetamino-^1.3.5(10)-estratriene in tricapryline and in glycerol were injected subcutaneously into mice. Tumors at the site of application were not observed; however, remote from the site of application an increased formation of tumors was observed. 3-Amino-^1.3.5(10)-estratrienol-(17) proved to be ineffective in the skinpainting-test on the mouse; in the feeding-test according to Huggins with female Sprague-Dawley-rats one mammary carcinoma appeared in 1 out of 10 animals. The results obtained so far should stimulate the investigation of representations of this class of compounds on a broader basis.—A hypothetical reaction sequence for the conversion of natural estrogens through their p-quinols into the amino-analogs (transamination with pyridoxamine-5-phosphate) is discussed.

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IV. Mitteilung s. Neumann und Thomas (1967).

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Die histologischen Untersuchungen wurden mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.     

Decreased mid-to-late diastolic decay of diastolic coronary artery flow velocity in pressure-overloaded left ventricular hypertrophy

Summary This study was carried out to investigate the characteristics of coronary arterial flow in left ventricular hypertrophy secondary to systemic hypertension. The blood velocities in the left anterior descending coronary artery (LAD) were measured by a No. 3F 20 MHz Doppler catheter in 23 hypertensive patients with left ventricular hypertrophy (systolic/diastolic pressure: 181 ± 15/100 ± 4 mmHg) and 13 patients with atypical chest pain, but without left ventricular hypertrophy and any abnormal hemodynamic findings. All patients had normal coronary arteriograms. The LAD blood velocity waveforms in pressure overloaded left ventricular hypertrophy were characterized by both a decreased mid-to-late diastolic deceleration rate (V/T) and a normalized value of V/T by peak diastolic velocity [V/(T · Vpeak)], as well as delayed early diastolic inflow (time for diastolic rise; TDR). The values of the V/(T · Vpeak) in the patients with hypertensive left ventricular hypertrophy and in the normotensive controls were 1.26 ± 0.61 and 3.03 ± 1.18/s, respectively (P < 0.001). The TDR was 145 ± 56 and 66 ± 15 ms (P < 0.001). In patients with hypertensive left ventricular hypertrophy, the V/(T · Vpeak) correlated well with the degree of hypertrophy (r = 0.75,P < 0.01) and with the TDR (r = 0.82,P < 0.01). The coronary flow reserve, calculated from the ratio of the diastolic mean velocity after intracoronary injection of papaverine to the resting flow velocity increased with the V/(T · Vpeak) (r = 0.68,P < 0.01). In conclusion, the increase in blood flow in the later part of diastole may compensate for the decrease in early diastolic inflow and may cause the reduction in the coronary flow reserve in pressure-overloaded LV hypertrophy.Supported, in part, by Kawasaki Medical School Grant (No. 1-102) for Project Research, Japan.     

Elastizitätsberechnungen am Modell des isolierten Ratten- und Katzenmyokards unter Kontrakturbedingungen an Hand von Ruhe-Dehnungs-Kurven

Summary Increase of Ca²⁺ concentration to 7.5 mM in the presence of 10 mM or 20 mM caffeine shifted length-tension relationships of 5 rat trabecular muscles and 5 cat papillary muscles to higher tensions. At l_max diastolic tension was enhanced from 1.18±0.17·10^–2N/mm² to 1.99±0.36·10^–2N/mm²(rat) and from 1.34±0.52·10^–2N/mm² to 2.64±0.65·10^–2N/mm²(cat). Stress (=F/A) and strain (=l–l₀/l₀) were calculated according toMirsky; and tangent modulus (E=d/d) was approximated by determination of / for all measured points of stress-strain relationships after the increase of diastolic tension by caffeine and Ca²⁺ as well as under control conditions. The function E=f()=b(–c) was computed by linear regression analysis (0.99>r²>0.96). The average value of constant b was 13.89±2.01 in control curves of rat trabecular muscles and 13.42±1.98 in curves with 10 mM caffeine and 7.5 mM Ca²⁺. Likewise, in cat papillary muscles 20 mM caffeine and 7.5 mM Ca²⁺ did not alter the stiffness constant b in a statistically significant manner (control: 16.63±3.03, caffeine: 16.43±3.02).The results demonstrate that the stiffness constant b cannot indicate acute variations of the length-tension relationship due to caffeine and Ca²⁺ and may result in overestimating of myocardial distensibility. However, if the tangent modulus (E) is related to strain (), the alterations of diastolic elasticity are detectable. Mathematical considerations of these experimental results imply a new base for evaluation of diastolic elasticity of the heart by means of the tangent modulus (E).These results are of substantial importance in clinical evaluation of distensibility of myocardial tissue, as the tangent modulus related to wall stress apparently is not appropriate to realize alterations in passive myocardial properties due to contracture.

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Elastizitätsberechnungen am Modell des isolierten Ratten- und Katzenmyokards unter Kontrakturbedingungen an Hand von Ruhe-Dehnungs-Kurven

Zusammenfassung Durch Zufuhr von 10 oder 20 mM Coffein und Steigerung der Ca²⁺-Konzentration auf 7,5 mM werden Ruhe-Dehnungs-Kurven von 5 Rattentrabekelpräparaten und 5 Katzenpapillarmuskeln zu höheren Spannungen hin verschoben. Bei der Muskellänge l_max steigt die diastolische Spannung im Mittel von 1,18±0,17·10^–2N/mm²auf 1,99±0,36·10^–2 N/mm²(Ratte) und von 1,34±0,52·10^–2N/mm²auf 2,64±0,65·10^–2N/mm²(Katze). Dem Vorschlag vonMirsky folgend, werden die Wertepaare der Ruhe-Dehnungs-Kurven durch die Begriffe Spannung (=F/A)und relative Muskellänge (=l–l₀/l₀) charakterisiert, und der tangentielle E-Modul in der Näherungsform / für alle Meßpunkte der Ruhe-Dehnungs-Kurven ermittelt. Die Funktion E=f()=b(–c) wird durch lineare Regression berechnet (0,99>r²>0,96). Die mittlere Steigung b in E=b(–c) beträgt für Kontrollkurven des Rattentrabekelpräparates 13,89±2,01 und 13,42±1,98 für die Kurven bei 10 mM Coffein und 7,5 mM Ca²⁺-Ionen-Konzentration. Im Katzenpapillarmuskel beträgt die durchschnittliche Steigung b unter Normalbedingungen 16,63±3,03 und 16,43±3,02 unter Kontrakturbedingungen. Die Ergebnisse demonstrieren, daß die Werte der Steigung b als Funktion der Spannung () einen veränderten Verlauf der Ruhe-Dehnungs-Kurve, bedingt durch Coffein und Ca²⁺-Ionen, nicht erkennen lassen und somit zu Fehlbeurteilungen der passiven Eigenschaften des Myokards führen können. Nur wenn die Werte des E-Moduls als Funktion der relativen Muskellägen (E=f[]) aufgetragen werden, sind die kontrakturbedingten Änderungen der passiven Gewebeeigenschaften erkennbar.Aus der mathematisch-analytischen Betrachtung dieser Ergebnisse resultiert ein neur Ansatz zur Bewertung der diastolischen myokardialen Steifheit auf der Basis des tangentiellen E-Moduls.Die Ergebnisse sind von klinischer Relevanz, weil sie zeigen, daß kontrakturbedingte Änderungen des elementaren Ruhe-Dehnungs-Verhaltens des Myokards auf Grund des spannungsbezogenen tangentiellen Elastizitätsmoduls nicht erkennbar sind.

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Mit 5 Abbildungen und 4 Tabellen

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Supported by the Deutsche Forschungsgemeinschaft.

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Herrn Prof. Dr.Bauereisen, Würzburg, zum 65. Geburtstag.     

Simultaneous evaluation of left- and right-sided heart pumping function during dynamic leg exercise in patients with mild chronic congestive heart failure, with special reference to afterload and plasma noradrenaline

Summary We simultaneously measured increases in mean pulmonary capillary wedge pressure (PCW), mean right atrial pressure (RA), and cardiac index (CI) in response to dynamic leg exercise in 81 patients with mild congestive heart failure to clarify the relationship between the left-sided and right-sided pumping function of the heart. The ratio of CI to PCW was used as an index of left-sided heart performance and the CI/RA as an index of right-sided heart performance. We also determined systemic vascular resistance, as an index of afterload on the left heart; pulmonary vascular resistance, as an index of afterload on the right heart; and the plasma level of noradrenaline before and during dynamic leg exercise. Patients with CI/PCW > 0.18l/min/m² per mmHg were regarded as having a well functioning left heart, and the patients with CI/PCW 0.18l/min/m² per mmHg as having a poorly functioning left heart. Patients with CI/RA > 0.311l/min/m² per mmHg were regarded as having a well functioning right heart, and those with CI/RA 0.311/l/min/m² per mmHg as having a poorly functioning right heart. Patients were classified into three groups: well functioning left and right heart (normal group;n = 40), poorly functioning left and right heart (bilateral group;n = 34), and poorly functioning left heart and well functioning right heart (left-sided group;n = 7). The systemic vascular resistance index decreased during leg exercise in all patients. The decrease was smaller in the bilateral group and the left-sided group than in the normal group. The pulmonary vascular resistance index increased during exercise in the bilateral group but was unchanged in the normal group and the left-sided group. The plasma level of noradrenaline increased during exercise in all patients, but the increase was greater in the bilateral and left-sided groups than in the normal group. Pretreatment with phentolamine, an -adrenoceptor antagonist, inhibited the increase in the pulmonary vascular resistance index and restored the decrease in the systemic vascular resistance index during exercise in the bilateral group. Our results showed that systemic vascular resistance, which represents afterload on the left heart, increased in the presence of impaired left-sided heart pumping function and pulmonary vascular resistance, which represents afterload on the right heart, increased in the presence of impaired right-sided heart pumping function. The inhibited decrease in systemic vascular resistance and the increase in pulmonary vascular resistance during exercise were associated with -adrenoceptor-mediated vasoconstriction caused by the increase in the plasma level of noradrenaline.     

Liver microsomal Δ6 and Δ5 linoleic acid desaturation in female BB rats

Summary Rat liver microsomal 6 and 5 desaturation are defective in experimental diabetes, but this defect is correctable with insulin treatment. Rat liver fatty acid composition and 6 and 5 desaturation were studied in the spontaneously diabetic adult female Bio-Breeding (BB) rat. Control Wistar rats and BB rats (4 weeks of diabetes), that received insulin (1 IU·100 g body weight^–1·day^–1), were killed 20 h after the last insulin injection. 6 and 5 desaturase activities were estimated from the incubation of liver microsomes with (1-¹⁴C) 18:2, n–6 or (2-¹⁴C) 20:3, n–6, respectively, and the fatty acid composition of the liver and microsomal liver lipids were investigated. Under experimental conditions 6 and 5 desaturase activities were unchanged in the BB rats when compared to the control rats. Impairment of the liver fatty acid composition of diabetic BB rats is not consistent with normal desaturase activity and may be explained by factors other than desaturation disturbance.     

Über Beziehungen zwischen Steroiden und krebserzeugenden Kohlenwasserstoffen

Zusammenfassung Die strukturellen Beziehungen zwischen Steroiden und krebserzeugenden Kohlenwasserstoffen sind durch die Klasse der 1:2-Cyclopentadieno-phenanthrene zu erweitern. ²-3-Methyl-1:2-cyclopentadieno-phenanthren und ¹-1-Methyl-1:2-cyclopentadieno-phenanthren sind im Pinselungstest an der Maus mäßig stark kiebserzeugend wirksam. Kohlenwasserstoffe dieses Typs entstehen bei der Dehydrierung von Cholesterin mit Chloranil (Tetrachlorchinon). Der Grund für die Wirksamkeit der 1:2-Cyclopentadieno-phenanthrene dürfte in der reaktionsfähigen Doppelbindung des Fünfringes liegen, die in diesem Falle als K-Region zu bezeichnen wäre.

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Summary The structural relationships between steroids and cancerogenic hydrocarbons are extended by the class of 1:2-cyclopentadieno-phenanthrenes. ²-3-methyl-1:2-cyclopentadieno-phenanthrene and ¹-1-Methyl-1:2-cyclopentadieno-phenanthrene are moderately cancerogenic in the mouse when tested by skin-painting technics. Hydrocarcons of this type are formed from the dehydrogenation of cholesterol with chloranile (tetrachlorquinone). The reason for the effectiveness of 1:2-cyclopentadieno-phenanthrene may well be due to the reactivity of the double bond of the five-membeved ring, which in this case would be designated as the K-region.

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Der Deutschen Forschungsgemeinschaft danke ich für eine Sachbeihilfe zur Durchführung dieser Arbeit.     

Niemann–Pick disease type C and defective peroxisomal β-oxidation of branched-chain substrates

An 18-month-old infant presented with hypotonia, motor delay, hepatosplenomegaly, rickets and steatorrhoea. Biochemical investigations revealed typical features of Niemann–Pick disease type C. In addition, there was evidence of defective peroxisomal -oxidation of branched-chain substrates (3,7,12-trihydroxycholestanoic acid and pristanic acid). The steatorrhoea and fat-soluble vitamin malabsorption responded well to bile acid therapy. Possible causes for the double defect are considered.     

Changes in the activity of ‘active’ pyruvate dehydrogenase complex in the newborn of normal and diabetic rats

Summary At birth, hepatic active and dichloracetate-activated pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar. The active and dichloracetate-activated pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p<0.05). The greatest increase in both active and dichloroacetate-activated pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats. Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of active pyruvate dehydrogenase complex activity within 1 h (p<0.01). Similar treatment caused no significant increases in the newborn of severely diabetic rats. The transient increases in active pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.     

Effects of short-term high dose intake of evening primrose oil on plasma and cellular fatty acid compositions, α-tocopherol levels,and erythropoiesis in normal and Type 1 (insulin-dependent) diabetic men

Summary In addition to their usual diet, nine Type 1 (insulin-dependent) diabetic men and ten male control subjects took 20 g d,ga-tocopheryl acetate enriched evening primrose oil (14.45 g 182c,6, 1.73g 183c,6, 400 mg d,-tocopheryl acetate) daily for one week. At start, diabetic patients had more 140, 150 and 18 2c,6, and less 160, 161c,7, 181c,7, 183c,6, 203c,9, 203c,6, 204c,6 and 226c,3 in plasma, erythrocytes and/or platelets. Furthermore, they had lower 161c,7/160, 181c,7/160, and 204c,6/203c,6 ratios and a higher 203c,6/183c,6 ratio. In diabetic patients, -tocopherol levels in erythrocytes were lower, whereas those in plasma were normal. In both groups, oil intake changed fatty acid profiles. Most markedly, 203c,6 increased, whereas the ratios 203c,6/ 183c,6 and 204c,6/203c,6 decreased. 204c,6 increased in control subjects, but not in diabetic patients. Erythrocytes and platelets responded differently in their fatty acid profiles, -tocopherol rose in plasma and, although less for diabetic patients, in erythrocytes. In diabetic patients as well as in control subjects, erythrocyte count, haemoglobin level, mean corpuscular haemoglobin content and concentration increased and glycosylated haemoglobin percentage decreased without an apparent decline in blood glucose levels. Plasma -thromboglobulin and platelet factor 4 decreased, especially in diabetic patients. In conclusion, diabetic patients had abnormal fatty acid patterns, suggesting an impaired 9, 6 and 5 desaturation and an enhanced chainelongation, and had lower erythrocyte a-tocopherol levels; and short-term high dose intake of evening primrose oil increased 203c,6 in both groups, but 204c,6 only in control subjects, gave fatty acid responses which were different for erythrocytes and platelets, enhanced erythropoiesis, and lowered indices of in vivo platelet activation.     

Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study

Aims/hypothesis Both insulin resistance and beta-cell dysfunction play a role in the transition from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM) through impaired glucose tolerance (IGT). The aim of the study was to define the level of glycaemia at which beta-cell dysfunction becomes evident in the context of existing insulin resistance.Methods Insulin response (OGTT) and insulin sensitivity (euglycaemic insulin clamp) were evaluated in 388 subjects in the San Antonio Metabolism (SAM) study (138 NGT, 49 IGT and 201 T2DM). In all subjects the insulin secretion/insulin resistance index (I/G÷IR) was calculated as the ratio of the increment in plasma insulin to the increment in plasma glucose during the OGTT divided by insulin resistance, as measured during the clamp.Results In lean NGTs with a 2-h plasma glucose concentration (2-h PG) between 5.6 and 6.6 and between 6.7 and 7.7 mmol/l, there was a progressive decline in I/G÷IR compared with NGTs with a 2-h PG less than 5.6 mmol/l. There was a further decline in I/G÷IR in IGTs with a 2-h PG between 7.8 and 9.3 and between 9.4 and 11.0 mmol/l, and in Type 2 diabetic patients with a 2-h PG greater than 11.1 mmol/l. Lean and obese subjects showed coincident patterns of relation of 2-h PG to I/G÷IR.Conclusion/interpreation When the plasma insulin response to oral glucose is related to the glycaemic stimulus and severity of insulin resistance, there is a progressive decline in beta-cell function that begins in normal glucose tolerant individuals.Abbreviations T2DM, Type 2 diabetes mellitus - FPG, fasting plasma glucose - 2-h PG, 2-h plasma glucose - EGP, endogenous glucose production - Ra, rate of appearance - TGD, total glucose disposal - IR, insulin resistance     

Survival of two patients with severe δ-aminolaevulinic acid dehydratase deficiency porphyria

The course of -aminolaevulinic acid dehydratase activity was studied over the 23 years in erythrocytes of two male patients. The enzyme activity was originally 1–2%, which then increased to 8% of normal levels several years after clinical manifestation of the acute hepatic porphyria syndrome. Urinary excretions of -aminolaevulinic acid and coproporphyrin III were excessively increased in the two patients with compound-heterozygous -aminolaevulinic acid dehydratase deficiency porphyria.     

γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

Summary Recently we described a cutaneous T-cell lymphoma expressing the / T-cell receptor [5]. The patient suffering from this lymphoma showed low numbers of myeloid and T cells in peripheral blood, while B and NK cells were relatively increased. In vitro culture of the patient's bone marrow (BM) cells revealed a significant suppression of myeloid/monocyte colony formation (GM-CFU) compared with normal controls. This was not due to infiltration of the BM with lymphoma cells. We speculated that a soluble factor either secreted or induced by the lymphoma cells might be responsible for the marked suppression of hematopoiesis in this patient. From a skin biopsy with infiltrating / T-lymphoma cells we established T-cell clones bearing the / T-cell receptor and resembling the phenotype of the lymphoma cells. The supernatant (SN) of these / T-cell clones reduced the number of colonies in a CFU-GM assay (using normal control BM) in comparison to SN of / T-cell clones established from the same biopsy. This suppression was seen mainly on day 7 of culture and was not neutralized by the addition of placenta-CM. The main mediator of this suppression seems to be IFN-,since it was detectable in high amounts in the SN of these / T-cell tumor clones as well as in the serum of the patient. In addition, anti-IFN- antibodies can reverse the T-cell SN-mediated suppression of CFU-GM. We conclude that high serum levels of interferon-, which is secreted in high amounts from / T-cells grown from a biopsy of a cutaneous lymphoma, can suppress hematopoiesis.Abbreviations TCR T-cell receptor - IFN- interferon- - SN supernatant - placenta CM placenta conditioned medium - BM bone marrow - CFU-GM myeloid/monocyte colony formation - NK cells natural killer cells - Ab antibody M. Wilhelm was supported by theDeutsche Forschungsgemeinschaft (DFG Wi 728-2)     

The JT-Area Indicates Dispersion of Repolarization in Dogs with Atrioventricular Block

Heterogeneity in cardiac repolarization (APD) is known to be arrhythmic. In the dog model of chronic complete AV-block and acquired long QT syndrome, an increase in MAPD (defined as left ventricular monophasic action potential duration (MAPD) minus right ventricular MAPD) is often associated with changes in T-wave morphology. The purpose of this study was to correlate known changes in MAPD with the planimetric total area of the T-wave on the surface ECG (_J^T,mV · ms). Methods: The relationship between MAPD and total area of the T-wave (i.e., JT-area) was assessed in four different protocols with different types of dispersion: (1) class III drugs followed by levcromakalim (n = 7), (2) LAD coronary artery occlusion and reperfusion (n = 6), (3) dronedarone i.v., an amiodarone like agent (n = 5) and (4) steady state pacing at cycle lengths of 1000 ms and 500 ms (n = 5). Results: Class III drugs increased MAPD (55 ± 40 ms to 120 ± 50 ms^#, P < 0.05), which was correlated (r = 0.74, P < 0.001) with JT-area (50 ± 40 mV · ms to 95 ± 35 mV · ms^#). Ischemia increased both MAPD (30 ± 25 ms to 90 ± 40 ms^#) and JT-area (60 ± 55 mV · ms to 75 ± 50 mV · ms^#). Both levcromakalim and reperfusion reversed these conditions. Dronedarone had no effect on MAPD or on JT-area while a faster frequency reduced both MAPD and JT-area. Conclusion: Changes in dispersion of ventricular repolarization are reflected by alterations in JT-area. This non-invasive parameter may therefore be used to indicate changes in heterogeneity in ventricular repolarization.     

Synthesis and evaluation of catechol analogs of diethylstilbestrol on a hormone-dependent human mammary carcinoma implanted in nude mice

Summary 3,4-Bis(3,4-diacetoxyphenyl)hex-3-ene (5a), 4(4-acetoxyphenyl)-3(3,4-diacetoxyphenyl) hex-3-ene (5b), and 4(3-acetoxyphenyl)-3(3,4-diacetoxyphenyl)hex-3-ene (5c) were synthesized according to the method of Dodds et al. (1939). All compounds inhibited the interaction of ³H-estradiol with its receptor. The relative binding affinity (RBA) values increased in the order: 5a (1.0)<5c (7.6)<5b (21.7). In the immature mouse uterine weight bioassay, the uterotrophic activity of 5a-c was only weak. 5a and 5c, but not 5b, exhibited significant antiuterotrophic properties. All compounds significantly inhibited the growth of a postmenopausal hormone-dependent human mammary carcinoma serially implanted in nude mice.Abbreviations COMT catechol-O-methyl transferase - ETOH ethanol - E2 estradiol - RBA relative binding affinity (E2=100) - LH luteinizing hormone - DMBA 9,10-dimethyl-1,2-benzanthracene Supported by grants from the Deutsche Forschungsgemeinschaft und Verband der Chemischen Industrie-Fonds der Chemischen Industrie     

Impaired alveolar gas exchange in acute pancreatitis

We evaluated the alveolar–arterial oxygen difference (A-a) and the ratio between P_ao₂ and the fractional concentration of inspired oxygen (P/F) in acute pancreatitis. Eleven patients had mild uncomplicated disease, six showed acute abdominal fluid collections, six had acute abdominal collections and asymptomatic x-ray lung involvement, three presented transient dyspneic episodes, and four had severe acute pancreatitis requiring prolonged oxygen therapy. In the uncomplicated disease, respiratory function was normal; in the six patients with abdominal collections only, A-a increased by 50% and P/F decreased by 20–30%; in the six patients with abdominal collections and asymptomatic x-ray lung involvement, A-a increased by 50–70% and P/F decreased by 40%; the three patients with dyspneic episodes showed a twofold increase in A-a and a 40% decrease in P/F; the four patients with severe pancreatitis had a two- to threefold increase in A-a and a 40–50% decrease in P/F. Hence respiratory function is normal only in uncomplicated pancreatitis; in the presence of complications, disturbance of gas exchange always occurs, requiring careful control and treatment.     

PBC-AIH overlap syndrome with concomitant ITP and Hashimoto’s disease with positivity for anti-centromere antibody

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimotos disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimotos disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6g/dl; -globulin (glb), 35.9%; total bilirubin (T-bil), 9.41mg/dl; direct bilirubin (D-bil), 7.52mg/dl; aspartate aminotransferase (AST), 957U/l; alanine aminotransferase (ALT), 651U/l; alkaline phosphatase (ALP), 595U/l; -guanosine triphosphate (GTP), 129U/l; IgG, 2620mg/dl; IgM, 223mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimotos disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.     

Spontane Blutdruckänderung und aortale Pulswellengeschwindigkeit bei Normotonikern

Zusammenfassung An 183 normotonen Männern im Alter von 17–74 Jahren zu Beginn der Langzeitstudie wurden im Zusammenhang mitspontanen Blutdruckschwankungen die davon abhängigen Änderungen der aortalen Pulswellengeschwindigkeit (PWG) über Jahre hin in zeitlichen Abständen erfaßt. Der Blutdruck durfte diastolisch 95 und systolisch 145 mm HG nicht überschreiten. Um den Altersgang der PWG zwischen 2 Messungen zur Gewinnung von reinen PWG-Mitteldruckbeziehungen (c-p-Beziehungen) auszuschalten, wurden vor dem 55. Lebensjahr 7 cm/sec pro Jahr, nach dem 55. Lebensjahr 9 cm/sec pro Jahr vom c-Wert der Zweitmessung abgezogen.DerDifferenzenquotient c_p als Maßstab für die Änderung von c mit dem Mitteldruck p ergibt sich aus der auf 10 mm Hg Druckänderung umgerechneten Differenz zwischen zwei zeitlich auseinander liegenden c-Werten (c₁–c₂) dividiert durch die Differenz der zugehörigen Mitteldruckwerte (p₁–p₂). Der Zeitfaktor hatte bei Durchführung der entsprechenden Alterskorrektur an c₂ keinen statistisch erkennbaren Einfluß auf c_p.In 78% der Fälle steigt und fällt c in unserer Langzeitstudie mit p, in 22% verhält sich die Änderung von c diskordant zur Änderung von p. Bei Berücksichtigungaller Versuchspersonen beträgt c_p im Durchschnitt 0,40 m/sec. Vor dem 55. Lebensjahr ist c_p kleiner (0,30 m/sec) als im höheren Alter (0,55 m/sec). Die Altersdifferenz von c_p ist signifikant (p=0,05). Bei alleiniger Berechnung derkonkordanten c-pBeziehungen beträgt c_p 0,70 m/sec und unterscheidet sich kaum von den früher publizierten c_p-Werten der Hypertoniker (0,60 m/sec; ebenfalls nur konkordante c-p-Beziehungen). Die im allgemeinen niedrigeren c_p-Werte ausGruppenquerschnitten (im Gegensatz zu den longitudinal geführten Untersuchungen) sind mit einer nicht erkennbaren Beimischung von diskordanten c-p-Beziehungen zu erklären.c_p erweist sich in einem p-Bereich von 90–170 mm Hg unabhängig von der Höhe des Ausgangsdruckes. Auch die Größe der (spontanen) Mitteldruckschwankung (5–70 mm Hg, NormotonikerHypertoniker) scheint keinen Einfluß auf den statistischen Mittelwert von c_p zu haben.c_p ist aber bei Normotonikern (ebenso wie bei Hypertonikern) abhängig von derRichtung der Blutdruckänderung, auch bei Berücksichtigung des Lebensalters. Bei Abnahme des Druckes ist c höher und c_p (p0,05) größer als bei Zunahme des Blutdruckes. Die c-p-Beziehung durchläuft demnach eine Art Schleife (entgegen dem Uhrzeigersinn).In der Diskussion wird der Einfluß der Gefäßmuskularis auf c_p aufzuzeigen versucht, der sich als roter Faden beim Vergleich der physiologischen c_p-Werte mit den c_p-Werten bei Arteriosklerose (Hypertonus; Diabetes) und bei Ausdauertraining anbietet. Daraus ist ableitbar, daß normale c- und c_p-Werte beiArteriosklerose darauf hinweisen, daß die Muskularis—selbst bei erheblichen regressiven Veränderungen der Gefäßwand—noch eine normale elastische Funktion aufrechtzuerhalten vermag.

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Spontaneous changes of blood pressure and aortal pulse wave velocity in normotensive subjectsResults of a long term study in 183 men

Summary The changes in the aortal pulse-wave velocity (PWV) occurring in connection with and dependent on spontaneous fluctuations of blood pressure has been recorded at intervals over the years in 183 normotensive men, who were aged from 17–74 at the beginning of the long term study. An essential condition was that the diastolic blood pressure should not exceed 95 mm Hg and the systolic 145 mm Hg. In order to eliminate the effect of age on the PWV between 2 measurements, and so to obtain a pure PWV-mean pressure relationship (c-p relationships), 7 cm/sec per year was subtracted from the c-value of the second measurement before the age of 55 and 9 cm/sec per year after that age.The differences quotient c_p as a standard for the change of c with the mean pressure p was obtained from the difference between two c values (c₁–c₂) taken at different times, converted to a pressure change of 10 mm Hg, and divided by the difference of the mean pressure levels belonging to them (p₁–p₂). In applying the appropriate age correction to c₂, the time factor had no statistically recognisable effect on c_p.In 78% of the cases in our long term study, c rose and fell with p, in 22%, the changes of c were at variance with the changes of p. Taking into consideration all the test subjects, c_p averaged 0.40 m/sec. Before the age of 55, c_p is smaller (0.30 m/sec) than above that age (0.55 m/sec). The age difference of c_p is significant (=0.05). When the concordant c-p relationships alone were calculated, c_p was 0.70 m/sec and scarcely differed from the c_p values of hypertensives published earlier (0.60 m/sec: also concordant c-p relationships only). The generally lower c_p values from group cross sections (in contrast to the longitudinal investigations) are explained by an unrecognisable admixture of discordant c-p relationships.In a range of pressure from 90–170 mm Hg, c_p was shown to be independent of the level of the initial pressure. Also the magnitude of the (spontaneous) mean pressure variation (5–70 mm Hg, normotensives—hypertensives) seems to have no effect on the statistical mean value of c_p.c_p is, however, dependent on the direction of the pressure change in normotensives (just as with hypertensives), even when age is taken into account. If the pressure is reduced, c is higher and c_p (p=0.05) is greater than when the blood pressure is increased. The c-p relationship traverses a kind of loop (counterclockwise).In the discussion, an attempt is made to point out the effect of the vascular musculature on c_p, which threads conspicuously through the comparison of the physiological c_p values with the c_p values in arteriosclerosis (hypertension; diabetes) and in endurance training. From this it can be deduced that normal values for c and c_p in arteriosclerosis indicate that the musculature is still capable of maintaining a normal elastic function even with considerable regressive changes in the vessel wall.

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Mit 4 Tabellen     

Human Leukocyte Interferon-α Treatment for Chronic HCV-Related Hepatitis in Hemophilic Patients Previously Intolerant to Other Interferons-α

Thirty patients affected by hemophilia A or B or von-Willebrand's disease and chronic posttransfusional active HCV hepatitis who developed major side effects during the course of a previous treatment with recombinant interferon- (IFN-) were studied. In all patients IFN- therapy had to be discontinued and those who achieved a primary serologic and viral response to HCV relapsed within a few months. After a washout period, patients were retreated with human leukocyte IFN-, 6 MU thrice weekly for 12 months. In about 90% of patients, a primary response, with normal AST and GGT values and undetectable HCV-RNA, was achieved within the third month of treatment and for the entire duration of treatment none of the patients had to discontinue therapy because of severe adverse reactions. During posttherapy follow-up only one patient relapsed. The human leukocyte IFN- regimen looks to be very effective and safe for carriers of inherited clotting disorders who developed major side effects with recombinant IFN- therapy for HCV-related chronic hepatitis.     

Oral glucose tolerance and ambient temperature in non-diabetic subjects

Summary When either a 960-kcal, 140-g carbohydrate meal, or a 75-g glucose load was ingested by non-diabetic Caucasians, the 2-h venous plasma glucose concentration was higher by 0.82 and 1.25 mmol/l, respectively, if the ambient temperature was 33 °C rather than 23 °C. It is likely that this is a result of relative arterialisation of the venous blood. Even at 23 °C room temperature, use of the hot hand technique to obtain arterialised venous blood increases post-load glucose levels in contralateral antecubital veins. If these observations apply to those acclimatised to the heat, they could affect the diagnosis of both diabetes and impaired glucose tolerance in the tropics.