Follow-up of “non-diabetic” relatives of diabetics by retesting oral glucose tolerance after 5 years

Summary Of 743 first degree relatives of diabetics in whom oral glucose tolerance tests had been performed in 1967 488 were re-tested in 1972. Among the original normals (n = 353) 17.6% had developed a subclinical and 1.3% an overt diabetes within 5 years. The original subclinical diabetics (n = 118) showed a remission to normal in 35.6% and a progression to overt diabetes in 13.6%. 3 out of the 17 formerly overt diabetics were found to be normal after 5 years and 3 were subclinical diabetics. Thus the performance of an oral glucose tolerance test is of limited prognostic value in the individual case. In both studies a higher prevalence of abnormal test results occurred in the older age groups and in overweight subjects. Remission or deterioration did not depend, however, on age or on weight changes. The frequency of abnormal tests was higher in males than in females, but the tendency towards the development of diabetes was more pronounced in females, in accordance with a previous observation of a higher age dependance of glucose tolerance in females.     

Ergebnisse physiologischer und psychologischer Untersuchungen bei verschiedenen Körperbautypen

Zusammenfassung Im Rahmen eines stationären Heilverfahrens wurden 210 männliche Patienten (Herzinfarkt, funktionelle Herz-Kreislauf-Störungen, Angina pectoris) untersucht, von denen 199 zur weiteren Auswertung herangezogen wurden, da von 11 Patienten nicht alle Körperbaumessungen vorlagen. Die Datenerhebung umfaßte zahlreiche anthropometrische Variablen und Indizes, kreislauf- und atemphysiologische Parameter, klinisch-chemische Befunde, Persönlichkeitstests und psychosoziale Daten. Vergleichbare Untersuchungen wurden, zwecks Reproduzierbarkeit, an 100 männlichen Studenten vorgenommen.Alle Körperbaumaße und Indizes unterliegen einem starken Alterseinfluß, der bei Nichtberücksichtigung zu altersbedingten Scheinkorrelationen zwischen Körperbau und anderen Variablenbereichen führen kann. Verschiedene Typisierungsversuche zeigten die Überlegenheit einer auf faktorenanalytischem Wege vorgenommenen Typisierung nach dem Fülle- und Größenfaktor.Es besteht ein lockerer Zusammenhang zwischen Körperbautyp und Krankheitsdisposition, wobei Infarktpatienten häufiger athletisch und pyknisch gebaut sind. Signifikante Unterschiede zwischen den Körperbautypen ergeben sich für den Blutdruck, die körperliche Leistungsfähigkeit, einige psychosoziale Daten und der Zuweisung zu heilverfahren. Keine Zusammenhänge ließen sich für Persönlichkeitsmerkmale und körperliche Beschwerden nachweisen.

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Results of physiological and psychological studies of different body typesA study of 210 patients with cardiovascular diseases and 100 students

Summary 210 male patients with myocardial infarction, functional cardiovascular diseases, and angina pectoris hospitalized in the course of a cardiac rehabilitation program had been studied. Missing data in some anthropometric variables reduced the sample to 199 patients. The body of data included various anthropometric variables and indices, parameters of the circulatory and respiratory systems, biochemical measures, personality questionnaires, and information about the psychosocial background. In order to replicate the findings a sample of 100 students was studied, too.The measures and indices of body type are influenced by age, which leads to age—dependent spurious correlations between body type and other variables if this dependency is not corrected. Different statistical approaches proved the superiority of a factor-analytic typisation based on a body-breadth and body-size factor. There is a low correlation between body type and disposition for certain diseases showing that patients with athletic or pycnic body build suffer preferably from coronary infarction. Significant differences between body types exist for blood pressure, physical fitness, several psychosocial data, and the number of previous courses of treatment. Correlations of body type with personality dimensions and bodily complaints did not occur.

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Mit 2 Abbildungen und 12 Tabellen

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Mit Unterstützung der Stiftung Volkswagenwerk und der Bundesversicherungsanstalt für Angestellte     

Phase contrast studies on mitotic cycle of pernicious anemia megaloblasts after vitamin B12 treatment

Summary Phase-contrast observations show that the mitotic time in vitro of erythropoietic cells (intermediate erythroblasts) from pernicious anemia patients 36 hours after the onset of Vit. B₁₂ therapy appears consistently longer than in megaloblasts from untreated patients. The duration of mitosis appears unchanged in erythropoietic cells from patients at the 4th day after the onset of treatment (definitive erythroblasts), in respect of intermediate erythroblasts. Both mitotic time of intermediate and definitive erythroblasts do not significantly differ from that of normoblasts from healthy patients. Maturation induces a lengthening of mitosis at a higher degree in intermediate, definitive and normal erythroblasts, than in megaloblasts. In connection with the increase in mitotic time, all mitotic phases are also prolonged, but at a different degree for each phase. These Authors claim that the proliferative potentials of intermediate, definitive, and normal erythroblasts are lower than that of megaloblasts from untreated patients.

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Zusammenfassung Phasenkontrastbeobachtungen zeigen, daß die Dauer der Mitose in vitro von erythropoetischen Zellen (intermediäre Erythroblasten) von Kranken mit perniziöser Anämie 36 Stunden nach Beginn einer Vit.-B₁₂-Behandlung durchwegs länger erscheint, als bei Megaloblasten von unbehandelten Kranken. Die Dauer der Mitose bei erythropoetischen Zellen von Kranken am 4. Tag nach Beginn der Behandlung (definitive Erythroblasten) scheint in bezug auf intermediäre Erythroblasten unverändert zu sein. Die Mitosezeit von intermediäre sowie von definitiven Erythroblasten unterscheidet sich nicht signifikant von der von Normoblasten gesunder Personen. Die Reifung verursacht eine Verlängerung der Mitose in höherem Maße bei intermediären, definitiven und der normalen Erythroblasten, als bei Megaloblasten. In Verbindung mit der Verlängerung der Mitosezeit werden auch alle Mitosephasen verlängert; jedoch in einem für jede Phase verschiedenen Ausmaß. Nach Ansicht der Autoren ist das Vermehrungspotential intermediärer, definitiver und normaler Erythroblasten niedriger, als das von Megaloblasten unbehandelter Kranker.

     

The ability of heat stress and metabolic preconditioning to protect primary rat cardiac myocytes

Primary rat cardiocytes were subjected to either thermal preconditioning for 30 min at 43°C or 20 min metabolic preconditioning (10 mM deoxyglucose, 20 mM lactate, pH 6.5). Eighteen hours later cells were analysed either for hsp 70i expression or subjected to a subsequent lethal heat stress or simulated ischaemia (10 mM deoxyglucose, 20 mM lactate, 0.75 mM sodium dithionite, 12 mM potassium chloride, pH 6.5) for 2 hours and assessed for survival by trypan blue exclusion.Hsp 70i was induced over 100 fold by thermal preconditioning and 30 fold by metabolic preconditioning (p<0.001, p<0.05), hsp 90 was induced 2.71 fold and 2.24 fold (p<0.001, p<0.001) by thermal and metabolic preconditioning respectively, while hsp 60 was not induced by either treatment. Preconditioned cultures had improved survival against subsequent lethal heat stress or simulated ischaemia: Thermal preconditioning reduced death from 69.22% to 52.46% upon subsequent lethal heat stress and from 49.13% to 36.66% upon subsequent lethal simulated ischaemia. Metabolic preconditioning reduced cell death from 51.29% to 33.8% against subsequent lethal heat stress, and from 69.09% to 55.61% upon subsequent lethal simulated ischaemia. A second marker of cell death, the release of lactate dehydrogenase activity into the culture media, was reduced to 65% and 60% of control values for thermally preconditioned cells subjected to lethal heat or lethal simulated ischaemia respectively. Metabolically preconditioned cells demonstrated lactate dehydrogenase activity of 59% and 51% that of control values, when subjected to lethal heat or lethal simulated ischaemia respectively.Abbreviations hsp heat stress protein - hsp 70i inducible 70 kDa heat stress protein - LDH lactate dehydrogenase - PBS phosphate buffered saline     

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Summary Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration (diffuse, cluster, and large) were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was diffuse in 18, cluster in 48, and large in 40 cases. RAEB-t patients accounted for about half of the large cases, and none had a diffuse pattern (p<0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by cluster blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of large cases (p<0.001) and in none of the cluster cases with severe BM fibrosis (p<0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with cluster BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.     

Histomorphologische und cytologische Befunde bei einem Fall von Gewebsmastzell-Retikulose mit akutem leukämieartigem Verlauf

Zusammenfassung Es wird über einen Krankheitsfall berichtet, welcher nach der bisherigen Nomenklatur als Gewebsmastzellen-Leukämie oder als maligne Mastocytose mit leukämieartigen Manifestationen (Efrati et al., 1957) bezeichnet worden ist; er muß als akute subleukämische Gewebsmastzellen-Reticulose klassifiziert werden.

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Summary The author reports a case which, according to the past nomenclature, was designated as tissue-mast-cell leukemia or as malignant mastocytosis with leukemia-like manifestations (Efrati et al., 1957). This case must be classified as an acute subleucemic tissue-mast-cell reticulosis.

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Vortrag auf dem 12. Kongreß der Deutschen Gesellschaft für Hämatologie, Berlin 1966.     

The antigenicity of human hemoglobins

Summary The correlation of the antigenicities among native hemoglobins and their subunit chains were investigated by the absorption of antisera and the combination of urea added immunoelectrophoresis with double diffusion. Alphachain showed identity with Hb-F but partial identity with -chain and Hb-A. Beta-chain showed identity with Hb-A but -chain and Hb-F showed partial identity with this chain. Gamma-chain showed identity only with Hb-F and its antigenicity was considered as being different from those of - or -chains.The lines of -, -and -chains were reconfirmed from the facts that the appearance of them depended always on the existence of anti-Hb-A or anti-Hb-F antibodies in the absorbed antisera and the minor component lines of

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Zusammenfassung Die Zusammenhänge der Antigenität zwischen nativen Hämoglobinen und deren Unterketten wurden mit der Absorption der Antiseren und der Kombination der Harnstoff-Immunelektrophorese und Doppeldiffusion untersucht. Die -Kette zeigte Identität mit Hb-F, aber nur partielle Identität mit der -Kette und Hb-A. Die -Kette war in ihrer Antigenität mit Hb-A identisch, die -Kette und Hb-F waren teilweise identisch mit der -Kette. Die -Kette zeigte die Identität mit Hb-F; es wird angenommen, daß ihre Antigenität verschieden von der -oder -Ketten ist.Für das Auftreten der Linien der -, - und -Ketten müssen Anti-Hb-A-oder Anti-Hb-F-Antikörper in den absorbierten Antiseren vorhanden sein, außerdem fusionieren die schwächeren Linien der Doppeldiffusion nicht mit irgendwelchen Linien der Unterketten. Auch gereinigte - oder -Ketten wurden zur Feststellung ihrer Linien benutzt.

     

The problem of thresholds in chemical carcinogenesis some views on theoretical and practical aspects

Conclusions I have tried to show that the threshold problem for carcinogens is still unsolved and that this unsatisfactory situation creates many problems for the scientific evaluation of the carcinogenesis problem as well as for its regulative aspects. In view of the extremely low acceptance of cancer risks in the general population, which is justified as well as understandable, carcinogenesis research must present new ideas to come nearer to a solution of such problems. More sound data on dose-time-effect curves in the low incidence range of 10-0.1% tumor incidences could indicated whether the established linearity in the higher incidence range might eventually by interrupted. Increase of animal numbers could also increase reliability of carcinogenicity experiments and allow the detection of low-dose effect; the disadvantages of this approach (mega-mouse experiment) however, in regard to cost and space necessary are evident. Increases of the mean life span by optimization of animal husbandry still would be another way of approach. However, no real breakthrough is to be expected here.The most promising approach seems to be the use of other indicators for carcinogenicity instead of tumor formation. Binding studies of carcinogens to biopolymers (Neumann 1980), especially DNA, as well as the determination of preneoplastic, enzyme-deficient islands (Kunz et al. 1978) have been shown to give dose-response curves parallel to the corresponding curves from carcinogenicity studies (Kunz) and extendable over 6 orders of magnitude of doses, without deviation from linearity (Neumann). Additional parameters might be found, which, altogether, might prove to be an important step toward further knowledge in this important field of carcinogenesis research.Oh König, das kann ich dir nicht sagen, und was du frägst, das wirst du nie erfahren R. Wagner, Tristan und IsoldeJournal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinicial oncology. These contributions represent exclusively the personal opinion of the author. The Editors Die Zeitschrift Journal of Cancer Research and Clinical Oncology bringt in zwangloser Folge Editorials und Guest Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autors wieder.     

Bone marrow and peripheral blood globin chain biosynthesis in iron deficiency

Summary Globin chain synthesis was studied in 13 iron-deficient patients. The mean whole-cell globin / ratio in the peripheral blood of 11 patients was 1.05±0.06 which is similar to the value 0.99±0.08 obtained for 10 controls. The ratios odtained for stroma-free globin were not significantly different from those of whole cell preparations. In contrast, the / ratio of bone marrow was 0.73±0.14 in 10 iron deficient patients, which is significantly lower than that of controls. Two other patients had decreased / ratios in the peripheral blood, probably because of the presence of an -thalassemia gene. These results demonstrate a reduced rate of synthesis of chains relative to that of chains in the bone marrow of iron-deficient patients that is not demonstrable in the peripheral blood.This work was partly supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil     

Die Arterienveränderungen beim Lupus erythematodes visceralis

Zusammenfassung Es werden an Hand von 5 Sektionsfällen die beim Lupus erythematodes visceralis auftretenden Arterienveränderungen an Milz, Nieren, Herz, Leber und Lungen eingehend untersucht und beschrieben. Als kennzeichnendes morphologisches Substrat der Arterienveränderung ergibt sich eine seröse bis fibrinöse und fibrinös-nekrotisierende Arteriitis ohne oder mit nur geringer entzündlicher Zellreaktion, die sich nicht zwanglos in die bekannten Formenkreise der Arteriitiden einordnen läßt, so daß die Herausstellung der Lupus-Arteriitis als Sonderform berechtigt erscheint. Auch die Milzarterien durchlaufen das Entzündungsstadium und vernarben mit einer zirkulär angeordneten perivaskulären Fibrose. Da die Gefäßveränderungen vorwiegend nur im akuten Stadium vorliegen, wird geschlossen, daß der Lupus erythematodes visceralis im fortgeschrittenen Stadium zu einer generalisierten Gefäßerkrankung wird und durch die dabei an lebenswichtigen Organen auftretenden Kreislaufstörungen zum Tode führt.Mit 7 Abbildungen in 14 Einzeldarstellungen     

Susceptibility and tolerance of β-lactamase-producing,methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins

Summary The activity of penicillin G, ampicillin, carbenicillin, ticarcillin, azlocillin, mezlocillin and piperacillin against 102 -lactamase-producing, methicillin-sensitive strains ofStaphylococcus aureus was determined by agar dilution (method A) and broth microdilution (method B) techniques. By NCCLS breakpoint criteria, 4% of the strains were sensitive to penicillin and ampicillin, and almost 100% were sensitive to the other drugs when method A was used. Results with method B were only significantly lower as far as the cumulative percentage of strains sensitive to azlocillin, mezlocillin and piperacillin was concerned (63–71%). Bactericidal effects at sensitive levels were observed in 0–2% (penicillin, ampicillin), 31–35% (carbenicillin, ticarcillin) and 10–14% (azlocillin, mezlocillin, piperacillin). While differences in MIC and MBC levels ranged from 0 to 8 dilution steps, tolerance (a >32-fold difference) was seen in at least 9–22% of all strains (depending on the drug tested); experimental limitations, however, excluded a determination of tolerance in all our strains. In a semi-quantitative nitrocefin assay, strong -lactamase production was correlated to high MIC and/or MBC levels.

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Sensibilität und Toleranz Betalaktamase-produzierender, Methicillin-sensibler Stämme von Staphylococcus aureus gegenüber sieben Breitspektrumpenicillinen

Zusammenfassung Die Aktivitäten von Penicillin G, Ampicillin, Carbenicillin, Ticarcillin, Azlocillin, Mezlocillin und Piperacillin gegen 102 -Lactamase-produzierende, Methicillin-sensible Stämme vonStaphylococcus aureus wurden mit Hilfe einer Agardilution (A) und Bouillon-Mikrodilution (B) bestimmt. Unter Zugrundelegung der NCCLS-Kriterien erwiesen sich bei Verwendung der Methode A 4% der Stämme als sensibel gegen Penicillin und Ampicillin und fast 100% sensibel gegen die anderen Penicilline. Mit Methode B ergaben sich signifikante Differenzen gegenüber A lediglich bei Azlocillin, Mezlocillin und Piperacillin (63–71% Sensibilität). Bakterizidie-Effekte im sensiblen Bereich ergaben sich bei 0–2% (Penicillin und Ampicillin), 31–35% (Carbenicillin und Ticarcillin) bzw. 10–14% (Azolocillin, Mezlocillin, Piperacillin). Differenzen zwischen MHK und MBK reichten von 0 bis 8 Verdünnungsstufen; und Toleranz (MBK> 32 MHK) wurde bei mindestens 9–22% der Stämme (je nach Antibiotikum) gesehen. Limitationen im Experiment ließen jedoch nicht bei allen Stämmen Auswertung auf Toleranz zu. Bei Verwendung einer semiquantitativen Nitrocefin-Bestimmungsmethode zeigte sich eine Korrelation zwischen starker -Laktamase-Produktion und hohen MHK- und/oder MBK-Werten.

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This paper is dedicated to Prof.Walter Siegenthaler on the occasion of his 60th birthday.     

Anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus investigated with a three-dimensional electroanatomical mapping system

We studied the anatomical structure of the isthmus between the inferior vena cava and tricuspid annulus in humans with a three-dimensional electroanatomical mapping system (CARTO, Biosense, Haifa, Israel). Fifteen patients with atrial flutter were studied. Thirteen patients had underlying heart disease. We investigated the anatomical structure of the isthmus with cross sections made from the three-dimensional right atrial map. The cross sections of the isthmus showed a concave shape in 7 patients (47%: group A), convex shape in 2 (13%: group B), and complex shape in 6 (40%: group C). The distance between the IVC and TA was 34 ± 17mm (group A), 25 ± 2mm (group B), 34 ± 16mm (group C), and 32 ± 15mm (Total), respectively. The distance between the top and bottom was 6 ± 5mm (group A), 3mm (group B), 6 ± 3mm (group C), and 6 ± 4mm (total), respectively. Seven of 15 patients exhibited an uneven surface of more than 5mm in depth and 4 of 15 patients had one of more than 10mm. The anatomical structure of the isthmus varies. To carry out precise catheter ablation, these variations should be taken into consideration to ensure an effective procedure.     

Transformation of morphological,functional and metabolic properties of fast-twitch muscle as induced by long-term electrical stimulation

Summary Transformation of structural, functional, metabolic and molecular characteristics is induced by stimulating fast-twitch muscles with the frequency pattern of a motoneuron normally innervating a slow-twitch muscle. These changes correspond to a transition of a fast-white into a slow-red muscle. Intermittent stimulation (8 h/d) does not affect the system but causes alterations of the sarcoplasmic reticulum which lead to changes in time to peak and half relaxation time. Continuous stimulation (24 h/d) induces a transformation of the muscle also at the level of the myosin system.

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Transformation morphologischer, funktioneller und metabolischer Eigenschaften schneller Muskeln durch langdauernde elektrische Reizung

Zusammenfassung Dauerstimulation schneller Muskeln mit dem Frequenzmuster langsamer Motoneurone induziert in schnellen Kaninchenmuskeln eine Transformation morphologischer, funktioneller, metabolischer und molekularer Merkmale. Diese Veränderungen entsprechen der Umwandlung eines schnellen/weißen in einen langsamen/roten Muskel. Intermittierende (8 Std/Tag) Stimulation bewirkt keine Umwandlung des Myosins, induziert aber eine solche des sarkoplasmatischen Retikulums. Kontinuierliche (24 Std/Tag) Stimulation bewirkt eine Transformation des Muskels, die auch eine Umwandlung des Myosins einschließt.

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Paper, presented at the Erwin Riesch Symposium, Tübingen, September 26–29, 1976

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With 3 figures

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This study was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 138 Biologische Grenzflächen und Spezifität.C. Heilmann ist postdoctoral fellow of the Deutsche Forschungsgemeinschaft.     

Single Capacitive Discharge Utilizing an Auxiliary Shock in the Coronary Venous System Reduces the Defibrillation Threshold

Auxiliary shocks (AS) from electrodes sutured to the left ventricle (LV) prior to primary biphasic shocks (PS) have been shown to reduce defibrillation thresholds (DFT). Two capacitors are required to generate these waveforms. We investigate delivery of AS from one capacitor using a novel waveform. The epicardial surface of the LV is accessed transvenously via the middle cardiac vein (MCV) avoiding a thoracotomy. Methods: A defibrillation electrode was placed in the right ventricle (RV) and superior vena cava (SVC) in 12 pigs (37±2kg). A 50×1.8mm electrode was inserted in the MCV through a guide catheter. A can was placed in the left pectoral region. A monophasic AS (100F, 1.5J) was delivered along one pathway before switching to deliver a biphasic waveform (40% tilt, 2ms phase 2) along another. DFTs (PS+AS) were assessed using a binary search. Two configurations not incorporating AS acted as controls. DFTs were compared using repeated measures analysis of variance. Results: DFTs of the four novel configurations (AS/PS) were: RVCan/MCVCan=14.9±3.7J, MCVCan/RVCan=17.2±5.7J, RVSVC+Can/MCVSVC+Can=13.4±4.6J, MCVSVC+Can/RVSVC+Can=17.1±5.9J. Delivering AS in the RV followed by PS in the MCV reduced the DFT (RVCan (19.9±7.3 J, P<0.01) and RVSVC+Can (19.2±6.0 J, P<0.05)). Conclusions: Delivering AS prior to PS in the MCV reduces the DFT by up to a third compared to conventional configurations of RVCan and RVSVC+Can. This is possible using only a single capacitor and an entirely transvenous approach to the LV.     

Ultrastructural features of the plasma cells in “non-secretory” myeloma

Summary A case of non-secretory multiple myeloma is described. The diagnosis was based on the clinical picture, typical radiological findings, and infiltration of the bone marrow by myeloma cells which showed specific immuno-fluorescence staining mainly with antisera for IgM and kappa light chains. An attempt is made to explain the absence of pathological proteins in the serum, based on the ultrastructural findings of the myeloma cells, which showed buddings of the cell membranes containing endoplasmic reticulum and cytoplasmic material. It is suggested that the cells of the non-secretory type of multiple myeloma possess a normal excretory mechanism, but the pathological proteins are prevented to be secreted in the serum being surrounded by portions of the cell membrane.Established Investigator of the Chief Scientist's Office, Ministry of Health, Israel     

Die sogenannten funktionellen Krankheiten des kardiovaskulären Systems als Syndrome der neurokardiovaskulären Inadaptation betrachtet

Ohne ZusammenfassungHerrn Prof. Dr.B. Kisch zum 70. Geburtstage gewidmet.Professor für Kardiologie in der Escuela Nacional de Medicina del Trabajo. Chef der Kardiologie-Abteilung in dem Ambulatorio Matias Montero des (S.O.E.) und des Instituto Nacional de Medicina del Trabajo in Madrid.     

The insulin response to glucose infusion in gestational diabetes

Summary Using a glucose infusion test insulin responses and insulin sensitivities were studied in 15 gestational diabetic women at 36–40 weeks gestation. In all women intravenous glucose tolerance had returned to normal at six weeks postpartum. Twelve women had a repeat glucose infusion test done 7–24 weeks (mean 17 weeks) postpartum. The results were compared with previously evaluated normal non-pregnant and normal pregnant standards and insulin responses below the normal 15^th percentile were defined as low. Twelve women had low insulin responses in late pregnancy, and six had low insulin responses postpartum. The mean insulin sensitivity index of 1.34±1.21 (mean ±SD) was significantly higher in the gestational diabetic group during pregnancy compared with a control pregnant group at 0.53±0.21 (p<0.01). The findings in this study support the hypothesis that gestational diabetes may arise in women who are unable to achieve adequate insulinogenic compensation to pregnancy. Increased insulin sensitivity in gestational diabetes may be a compensatory mechanism.     

Detection of anti-bovine β2-glycoprotein I antibody in sera from patients with antiphospholipid syndrome

We studied and characterized anti-bovine ₂ I antibodies (aB₂-GPI) in sera from patients with antiphospholipid syndrome (APS) by ELISA. Bovine ₂-glycoprotein I ₂-GPI was purified by heparin affinity and DEAE ion-exchange chromatography, and identified on immunoblots using a monoclonal antibody against human ₂-GPI and by amino acid sequence analysis. aB₂-GPI levels in the sera from 36 APS patients were measured by ELISA using purified bovine ₂-GPI as an antigen. The mean±standard deviation level of aB₂-GPI was 17.4±22.0 units in the 58% of APS patients who were positive. There was a significant correlation (P=0.003) between aB₂-GPI and anticardiolipin antibody (aCL) levels. aB₂-GPI from the sera of patients with APS was inhibited by bovine ₂-GPI itself. Purified IgG from the sera of patients with APS showed that bovine ₂-GPI was capable of acting as a cofactor for aCL. Purified bovine ₂-GPI was useful antigen for conventional ELISA. aB₂-GPI may contribute to the further development of aCL analysis and to the understanding of the pathogenesis of APS.     

Heparin attenuates low-dose streptozotocin-induced immune diabetes in mice and inhibits the Beta-cell binding of T-splenocytes in vitro

Summary Five low doses (40 mg·kg^–1·day^–1) of streptozotocin were given to CD-1 mice to induce immune diabetes with insulitis. T-splenocytes (L3T4⁺ and Lyt 2⁺) from streptozotocin-treated mice were previously reported to display in vitro an increased binding for Beta cells, preceding the onset of hyperglycaemia and of insulitis. Since heparin inhibits lymphocyte traffic, displays anti-adhesive properties, and attenuates some cell-mediated immune diseases, we have investigated the effects of heparin and N-desulphated heparin: 1) in vivo on low-dose streptozotocin-induced diabetes and insulitis, and 2) in vitro on the increased binding of T-splenocytes from streptozotocin-treated mice to rat insulinoma (RINm5F) cells. Daily subcutaneous low doses (5 g or 10 g) of heparin induced a delay in onset and a reduction of the severity of hyperglycaemia and insulitis (p < 0.01), and reduced the incidence of diabetes (p < 0.01). Similar effects swere obtained with 5 g daily doses of N-desulphated heparin devoid of anticoagulant activity. In contrast, lower (1 g) or higher (200 g) doses of heparin were ineffective. Heparin (10 g) did not modify the toxic diabetes induced by a single high dose (200 mg/kg) of streptozotocin. On the other hand, heparin dose-dependently (0.1 g/ml to 500.0 g/ml) inhibited the increased binding of splenocytes from streptozotocin-injected mice to RIN cells as compared to splenocytes from control mice. This in vitro anti-adhesive effect was detected when either splenocytes or RIN cells were pretreated with heparin before their co-incubation, and was also obtained with N-desulphated heparin. Heparinoids display anti-adhesive and immunomodulatory properties that are of therapeutic potential in this model of Type 1 (insulin-dependent) diabetes mellitus.     

Inorganic phosphate inhibits contractility and ATPase activity in skinned fibers from human myocardium

Summary During hypoxic heart failure, inorganic phosphate (Pi) accumulates. We report the effects of Pi on force development and on myofibrillar ATPase-activity of human skinned atrial fibers, both at normal and at reduced levels of Mg-ATP. Pi (10 mM) depressed force production at maximal calcium activation (pCa 4.3) by about 40%. At higher pCa values (pCa 5.6), foree inhibition was even more pronounced, but at low concentrations of Mg-ATP (10 M), Pi was less effective. In contrast to contractile force, myofibrillar ATPase was only inhibited by about 10% at pCa 4.3, whereas it could be inhibited by 40–50% at submaximal calcium activation (pCa 5.6). As Pi inhibited contractile force more than ATPase activity, the ratio of ATPase-activity to foree (tension cost) was increased by inorganic phosphate. ATPase-activity and tension cost were significantly reduced by loweing Mg-ATP concentration to 10 M, whereas contractile force was less affected. Pi did not affect ATPase under these conditions at 10 mM Mg-ATP. Pi also shifted the calcium-force relationship towards higher Ca⁺⁺ concentrations, that is, it decreased calcium sensitivity. In contrast, the calcium sensitivity of myofibrillar ATPase was less affected. These findings suggest that inorganic phosphate may affect the myocardium by altering crossbridge kinetics rather than the calcium affinity of troponin-C. Because of its inhibitory effect on myofibrillar ATPase, inorganic phosphate may be partly cardioprotective in the hypoxic myocardium. However, this energy sparing effect is probably offset by the greater tension cost that decreases the efficiency of tension maintenance in the presence of inorganic phosphate.