Cineangiographic evaluation of changes in regional left ventricular wall motion after acute myocardial infarction

Summary To evaluate the natural course of changes in regional left ventricular function after acute myocardial infarction, we compared cineventriculograms taken during the acute and chronic stages of myocardial infarction in ten patients who had sustained coronary occlusion despite intracoronary thrombolysis. Three ventricular silhouettes (end diastole, aortic valve opening, and closure) were superimposed using external reference markers, and 36 radial grids were drawn from the center of gravity of the end-diastolic silhouette to the endocardial margin of each silhouette. Measurement of the length of each radial grid provided quantitative details of segmental centripetal wall motion. In the infarcted area, percentage total systolic shortening (%LTOT), isovolumic shortening (%LISO), and ejection phase shortening (%LEJ) remained unchanged. In the nonischemic area, %LTOT tended to increase from 34%±6% to 41%±6%. Although %LISO was unchanged (9%±4% vs. 8%±1%), %LEJ increased from 25%±4% to 37%±6% (P<0.05). Thus, progressive increases in ejection phase shortening in normal regions may contribute to the functional recovery of the left ventricle after myocardial infarction.     

K-value and low insulin secretion in a non-obese white population: predicted glucose tolerance after 25 years

Aims/hypothesis Insulin resistance and insulin deficiency are proposed as risk factors for IGT and type 2 diabetes. We assessed the predictive value of initial parameters for the outcome of an OGTT performed 24.3±2.9 years later in an unselected healthy non-obese population.Methods The K-value of an IVGTT was determined in 267 healthy subjects (mean±SD: age 31.0±12.0 years, BMI 21.8±2.8 kg/m²). First-phase insulin response to a glucose infusion test was estimated as an incremental 5- or 10-min (I5 or I10) value, and as insulinogenic indices (I5/G5 or I10/G10) adjusted for insulin sensitivity determined by homeostasis model assessment for insulin resistance ([I5/G5]/HOMA-IR).Results At follow-up, six subjects had type 2 diabetes and 47 had IGT; 214 retained normal glucose tolerance. Insulin sensitivity and early (30 min) insulin response decreased with decreasing outcome OGTT. Blood glucose (2 h) at OGTT correlated positively with initial age and BMI, and negatively with I5/G5, (I5/G5)/HOMA-IR and K-value. In multiple linear regression analysis, (I5/G5)/HOMA-IR, I10, K-value, age, HOMA estimate of insulin secretion, and fasting plasma glucose were significantly associated with 2-h OGTT blood glucose. Similar results were obtained on comparing differences between subjects with normal and decreased (IGT+diabetes) glucose tolerance.Conclusions/interpretation In 267 non-obese healthy subjects, initial K-value and first-phase insulin response to glucose adjusted for insulin sensitivity, but not insulin sensitivity itself, were strong predictors of the outcome of an OGTT performed 25 years later. Thus, in contrast to obese or other high-risk populations, in lean subjects, decreased beta cell function, but not insulin resistance itself, determines future glucose tolerance.This paper is dedicated to Rolf Luft, our mentor and collaborator over several decades, on the occasion of his 90th birthday.     

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.     

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.     

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.     

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.     

Pleural pressure measured in the zone of apposition of diaphragm to rib cage in rabbits

In 10 anesthetized adult rabbits, we studied the effect of spontaneous breathing and positive pressure ventilation on pleural pressure on the costal lung surface (P_pl) and in the zone of apposition of the rib cage to the diaphragm (P_app). P_pl and P_app were measured by rib capsules installed in the 5th or 6th rib and 11th or 12th rib, respectively. Esophageal (P_es) and gastric (P_ga) pressures were measured with air-filled balloons. At end expiration (functional residual capacity), P_pl was subatmospheric (–2.5 ± 1.4 cm H₂O), decreased during spontaneous inspiration, and was in phase with P_es. In contrast, P_app was above atmospheric pressure (2.1 ± 1.8 cm H₂O), increased during inspiration, and was in phase with P_ga. P_app lagged P_pl by 180° during spontaneous inspiration but was in phase with P_pl during mechanical ventilation. Changes in P_pl (P_pl) during inspiration were greater in magnitude than either P_app or P_ga. Changes in transdiaphragmatic pressure in the zone of apposition (P_ga - P_app) were near zero (–0.4 ± 0.3 cm H₂O), much smaller in magnitude than those (P_ga - P_pl) associated with the lung (3.0 ± 1.5 cm H₂O). These results are consistent with the concept that during breathing, abdominal pressure is transmitted to the zone of apposition of the rib cage to the abdomen. During spontaneous breathing at rest, the pleural space in the zone of apposition is mechanically independent of the pleural space associated with the lung. Offprint requests to: Stephen J. Lai-Fook     

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.     

Demonstration of a relatively hepatoselective effect of covalent insulin dimers on glucose metabolism in dogs

Summary Insulin analogues with relatively greater effect on hepatic glucose production than peripheral glucose disposal could offer a more physiological approach to the treatment of diabetes mellitus. The fact that proinsulin exhibits this property to a minor degree may suggest that analogues with increased molecular size may be less able than insulin to obtain access to peripheral receptor sites. Covalent insulin dimers have previously been shown to possess lower hypoglycaemic potencies than predicted by their in vivo receptor binding affinities. Reduced rates of diffusion to peripheral target tissues-might be an explanation for the lower in vivo potency compared to insulin. To test the relative hepatic and peripheral effects of covalent insulin dimers, glucose clamp procedures with D-[3-³H] glucose tracer infusions were used in anaesthetised greyhounds to establish dose-response curves for rates of hepatic glucose production and glucose disposal with insulin, N^B1, N^{B 1},-suberoyl-insulin dimer, and N^B29, N^{B 29},-suberoyl-insulin dimer. With N^B1, N^{B 1},-suberoyl-insulin dimer molar potencies relative to insulin were 68%, (34–133) (mean and 95% fiducial limits), for inhibition of hepatic glucose production and 14.7%, (10.3–20.9) for glucose disposal. With N^B29,N^{B 29},-suberoyl-insulin dimer potencies were 75%, (31–184) and 2.5%, (1.5–4.3), for inhibition of hepatic glucose production and for glucose disposal, respectively. The demonstration that both dimers exhibit a significantly greater effect on glucose production than on glucose disposal supports the suggestion that analogues with increased molecular size may exhibit reduced ability to gain access to peripheral target cells.Abbreviations B1-B 1D N^B1,N^{B 1},-suberoyl-insulin dimer - B29-B 29D N^B29,N^{B 29},-suberoyl-insulin dimer - Ra hepatic glucose production rate - Rd peripheral glucose disposal rate - M_r relative molecular weight - MCR metabolic clearance rate - ANOVA analysis of variance     

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.     

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.     

Total life consumption of cigarettes as a determinant of coronary artery disease documented by coronary arteriography

The present study investigated the role of cigarette consumption as a clinical indicator of significant coronary artery disease, an application hitherto considered unrealistic. The study was done in two parts: (1) case control men (n=96) with coronary artery disease and men with normal coronary arteries of identical ages (n=96); (2) consecutive patients (n =1016–913 males and 103 females) subjected to diagnostic coronary arteriography and Bruce treadmill exercise testing. Significant coronary artery disease was defined as diameter stenosis =70% for any coronary branch, except for left main stem =50%. Exercise positivity was defined as ST = 1 mm or ST 1 mm in leads without pathological Q waves. It was found that (1) patients with significant coronary artery disease were differentiated significantly (p < 0.001) from persons with normal coronary arteries by the life consumption of cigarettes (pack-years) independently of their age; (2) heavy smoking (>30 packyears) in male patients without a history of typical angina pectoris subjected to coronary arteriography is diagnostically equivalent to electrocardiographic positivity of exercise testing; (3) in the same context, smoking of any quantity in women is diagnostically equivalent to positive exercise testing. It was concluded that among patients addressed for diagnostic coronary arteriography and devoid of history of typical angina pectoris, smoking for women and heavy smoking for men is diagnostically equivalent to positive exercise testing.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Influence of anti-ulcer drugs used in Japan on the result of <Superscript>13</Superscript>C-urea breath test for the diagnosis of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection

Background The ¹³C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.Methods The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H₂-receptor antagonist (H₂RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21.Results The mean ¹³C in the lansoprazole group was significantly decreased on day 14, to below 10, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the ¹³C falling to 1.7. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean ¹³C showed a tendency to decrease after the administration of ecabet sodium and rebamipide.Conclusions Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone.     

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass

Aims/hypothesis The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass.Methods A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic–hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (% L: H).Results Preoperative % L: H showed a significant (p=0.0009, r²=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r²=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, % L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account.Conclusions/interpretation The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic–hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reduction.     

Über Beziehungen zwischen Steroiden und krebserzeugenden Verbindungen

Zusammenfassung Eine Reihe künstlicher Oestrogene und krebserzeugender Amine haben das gleiche aromatische Grundskelet, unterscheiden sich aber durch ihre funktionellen Gruppen: Hydroxylgruppen bedingen oestrogene, Aminogruppen dagegen krebserzeugende Wirkung. Zur Prüfung, ob diese Gesetzmäßigkeit auch für die natürlichen Oestrogene gilt, wurden diesen nahestehende Aminoverbindungen, 3-Amino-4-methyl-^1.3.5(10)-oestratrienol-(17) und 2-Amino-4-methyl-^1.3.5(10)-oestratrienol-(17) auf krebserzeugende und oestrushemmende Wirkung untersucht. Während die 3-Amino-verbindung im Injektionstest an der Maus (nicht aber im Fütterungstest an der jungen weiblichen Sprague-Dawley-Ratte nach Huggins) eine schwache krebserzeugende Wirkung zu haben scheint, ist die 2-Aminoverbindung unwirksam. Keine der beiden Aminoverbindungen wirkt oestrogen oder oestrushemmend

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Summary A series of synthetic estrogens and cancerogenic amines have the same basic aromatic configuration; they differ, however, in their functional groups: hydroxyl groups imply estrogenic effect, whereas amino groups mean cancerogenic effect. To test whether this rule applies also for the natural estrogens, the closely related amino compounds, 3-Amino-4-methyl-^1.3.5(10)-estratrienol-(17) and 2-Amino-4-methyl-^1.3.5(10)-estratrienol-(17), are tested for their cancerogenic and estrus-inhibiting effects. Whereas the 3-amino compound appears to have a weakly cancerogenic effect when injected into the mouse (not, however, according to Huggins in feeding studies on young female Sprague-Dawley rats), the 2-amino compound is inactive. Neither of the amino compounds is estrogenic or inhibitory for estrus.

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Mit 2 Textabbildungen

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Herrn Prof. Dr. A. Butenandt zum 60. Geburtstag gewidmet.     

Capsular and ‘O’ serotype determinants of Bacteroides fragilis

Summary Forty-one strains ofBacteroides fragilis, 20 strains of otherBacteroides species and 14 strains of other genera were examined by the indirect immunofluorescent assay (IFA) using anticapsular serum. The sixty-oneBacteroides strains were O serotyped by direct agglutination tests using absorbed antisera raised against 23 strains, each with a different O antigenic determinant. All 41B. fragilis strains tested were positive by IFA with the anticapsular serum, but apart from one strain ofB. distasonis, none of the remaining 19 strains of other bacteroides, i. e.B. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus group andB. ureolyticus, and none of the 14 other bacterial species examined were positive. The majority of strains of saccharolytic bacteroides tested reacted with one of the 23 O antisera and were designated as a specific O serotype; a fewBacteroides strains had multiple agglutination reactions indicating the presence of multiple antigenic determinants. All O serotypes gave positive IFA tests with their homologous O antisera. Common capsular determinants and O antigenic determinants appear to exist on the same strains ofB. fragilis. Serological typing ofB. fragilis and related species would be useful in epidemiological studies.

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Kapsel- und O-Determinanten von Bacteroides fragilis

Zusammenfassung 41 Stämme vonBacteroides fragilis, 20 Stämme andererBacteroides-Spezies und 14 Stämme anderer Genera wurden unter Verwendung von Kapsel-Antiserum mit dem indirekten Immunfluoreszenztest (IFA) untersucht. Die O-Serotypisierung der 61Bacteroides-Stämme erfolgte mit dem indirekten Agglutinationstest; dabei wurden absorbierte Antiseren gegen 23 Stämme verwendet, von denen jeder eine unterschiedliche O-Determinante aufwies. Alle untersuchten 41 Stämme vonB. fragilis waren im IFA mit Kapsel-Antiseren positiv; hingegen war mit Ausnahme eines Stammes vonB. distasonis keiner der übrigen Stämme andererBacteroides-Spezies positiv, das heißt der GruppeB. thetaiotaomicron, B. distasonis, B. vulgatus, B. ovatus, B. melaninogenicus undB. ureolyticus; von den anderen geprüften 14 Bakterienspezies war ebenfalls keine positiv. Die Mehrzahl der Stämme der untersuchten saccharolytischenBacteroides reagierte mit einem der 23 O-Antiseren und wurde einem spezifischen O-Serotyp zugeordnet; einigeBacteroides-Stämme wiesen mehrfache Agglutinations-reaktionen auf, was für das Vorliegen mehrerer Antigendeterminanten spricht. Bei denselben Stämmen vonB. fragilis scheinen gemeinsame Kapsel- und O-Antigendeterminanten vorzukommen. Für epidemiologische Untersuchungen dürfte die Serotypisierung vonB. fragilis und verwandten Spezies von Nutzen sein.

     

Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors

Summary Objective: Although Selective Serotonin Reuptake Inhibitors (SSRIs) are important antidepressant drugs, knowledge of their vaso active effects is limited. Vaso active effects of the SSRI sertraline were studied in rings of rat aorta, human Internal Mammary Arteries (IMAs) and in Langendorff perfused rat hearts.Methods: The effects of sertraline (0.1 to 300 mol L^{– 1}) on precontracted rat aortic and IMA rings were evaluated in organ bath chambers. Precontraction was elicited by serotonin (5-HT; 10 mol L^{– 1}), phenylephrine (PE; 10 mol L^{– 1}) and potassium chloride (KCl; 50 mmol L^{– 1}). In addition, the effects of sertraline on PE induced contraction curves were established by subjecting vascular rings to increasing doses of PE (1 nmol L^{– 1} to 10 mol L^{– 1}) in the presence of sertraline or vehicle. Finally, the effects of sertraline on ex vivo coronary flow in rat hearts were examined using a retrograde Langendorff perfusion model.Results: Sertraline elicited dose-dependent relaxation, independent of the substance used for precontraction (p < 0.025). Sertraline showed a rightward shift of dose-response curves to PE (p < 0.01). Vasodilatory effects of SSRIs were endothelium independent. In perfused rat hearts, sertraline (0.3 to 10 mol L^{– 1}) showed a concentration-dependent increase in coronary flow that returned to baseline levels after wash-out of the antidepressant (p = 0.005).Conclusions: One of the SSRIs, sertraline, showed marked vasodilatory effects in rat aorta and human IMAs. Sertraline elicited vasodilatation in coronary arteries during perfusion of rat hearts. These hemodynamic effects may explain the observed beneficial effects in myocardial ischemia and infarction.     

Early prognosis after thrombolysis: value of exercise radionuclide ventriculography performed on anti-ischaemic medication

We examined the prognostic value of exercise radionuclide ventriculography (RNV) performed on anti-ischaemic medication following thrombolysis. Within 3 months of thrombolysis for first myocardial infarction, 31 medically treated patients with revascularisable but non-critical and minimally symptomatic coronary disease had left ventricular ejection fraction (LVEF) measured by first-pass exercise RNV. This was first performed off treatment and then repeated within 4 weeks on patients' regular medication. Follow-up at 12 months post-thrombolysis showed that 5 patients (Group I) had suffered significant recurrent symptoms (worsening angina requiring revascularisation in 3, unstable angina in 1, reinfarction in 1), but 26 remained well (Group II). Both groups were similar in age, post-thrombolytic severity of coronary disease, exercise LVEF whether off (39%vs 43%) or on medication (43%vs 44%), and change in LVEF with exercise (LVEF) off medication (–11%vs –3%). However, on medication, there was a significant difference in mean LVEF between Groups I and II (–11%vs+5%,P=0.0008, 99% confidence interval=4 to 26%).Thus, following thrombolysis, an abnormal LVEF despite anti-ischaemic medication may identify patients at risk of significant early recurrent ischaemia. Post-thrombolysis prognostic testing by exercise RNV may therefore be of greater value when performed on rather than off medication.     

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     

Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells

Summary Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of ⁷-PGA was most marked, followed by that of ¹²-PGJ₂, PGJ₂ and PGD₂. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ₂ and ¹²-PGJ₂ alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with ¹²-PGJ₂, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD₂ or ⁷-PGJ₁, compared to the results in groups treated with PGD₂ alone, ⁷-PGJ₁ alone or cisplatin alone. Combination of PGJ₂ or ¹²-PGJ₂ and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD₂ or ⁷-PGJ₁ with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.Abbreviation Cisplatin cis-diamminedichloro-platinum(II) This work was supported in part by a grant-in-aid for comprehensive ten year strategy for cancer control from the Ministry of Health and Welfare of Japan (Y.K. and M.F.)