Serum cytokines in patients with rheumatoid arthritis

Serum cytokines such as interleukin 1 (IL-1), interferon (IFN-), and tumor necrosis factor (TNF) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1 was detected in 5 patients, IFN- in 10 patients, and TNF in 20 patients. The IL-1-positive group showed increased values of activity indices compared to the IL-1-negative group. Values of serum IFN- correlated well with the number of peripheral blood lymphocytes and CD3⁺ cells and with the percentage of CD3⁺ CD26⁺ cells. Values of serum TNF correlated positively with the number of peripheral blood monocytes and the percentage of CD3⁺ HLA-DR⁺ and CD3⁺ CD25⁺ cells. These results indicated that serum IL-1 in RA patients reflects the activity of RA, while the serum IFN- and TNF in RA patients may be related to circulating activated lymphocytes and monocytes, respectively.     

Comparative and combined effects of transforming growth factors α and β, interleukin-1 and interferon-γ on rheumatoid synovial cell proliferation,glycolysis and prostaglandin E production

Summary Enhanced cell proliferation, glycolysis and prostaglandin E production are all characteristic features of rheumatoid synovial tissue. The interrelationships of these three cellular parameters have been examined using rheumatoid synovial fibroblasts and their responses to specific cytokines in vitro. Transforming growth factor (TGF) caused a more than threefold increase in synovial cell proliferation whilst transforming growth factor (TGF), interleukin-1 (IL-1) and interferon- (IFN-) produced only marginal changes. The combined addition of IL-1 with TGF resulted in an enhanced proliferative response comparable with that produced by TGF. Glycolysis, estimated by glucose utilisation and measurements of the glycolytic regulatory metabolite fructose 2,6-bisphosphate was significantly stimulated by TGF, IL-1 and IFN-, but less so by TGF. Prostaglandin E production was significantly increased by IL-1 to an extent much greater than that produced by TGF or TGF, although the combined addition of IL-1 with either TGF or resulted in a synergistic increase in PGE production, a response partly diminished by the addition of IFN-. These findings suggest that the extent to which a cytokine stimulates glycolysis is not consistently related to its mitogenicity, and that cytokine combinations which stimulate high levels of PGE production (a growth inhibitor) will not necessarily be associated with a reduced rate of cellular proliferation in cultured, adherent, rheumatoid synovial fibroblasts.     

Lymphozytenisolierung aus dem Blut des Menschen und der Tiere

Zusammenfassung Nach Diskussion der verschiedenen Verfahren zur Gewinnung von Leukozyten und Lymphozyten wird eine Methode für die Reinisolierung von Lymphozyten aus dem Blut von Mensch, Pferd, Rind, Schaf, Schwein und Hund beschrieben. Die Methode beruht auf den unterschiedlichen spezifischen Gewichten der Blutzellen, wobei Jodamid und jodamidhaltige Präparate Verwendung finden. Bei den Untersuchungen haben sich besonders die jodamidhaltigen Röntgenkontrastmittel Uromiro-300 und Uromiro-380 bewährt.

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Summary After the discussion of the different methods for obtaining leucocytes and lymphocytes a method is described concerning the pure isolation of lymphocytes out of the blood of humans, horses, cattle, sheep, pigs and dogs. The method is based on the different specific weights of the blood cells. Jodamid and jodamid-compounds were used for this purpose. The X-ray-contrast media Uromiro-300 and Uromiro-380 containing both jodamid turned out to be especially effective.

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Die Arbeit wurde mit Unterstützung der Deutschen Forschungsgemeinschaft durchgeführt.     

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.     

Presence of Two Signaling TGF-β Receptors in Human Pancreatic Cancer Correlates with Advanced Tumor Stage

Transforming growth factor- (TGF-)signal transduction is mediated via specific cellsurface signaling TGF- receptors, most notably thetype I ALK5 (TR-I_ALK5)and the type II(TR-II). We evaluated TR-I_ALK5 andTR-II expression in 41 human pancreatic cancertissue samples and correlated these findings withclinical data of the patients. Northern blot analysisindicated that, in comparison with the normal pancreas,pancreatic adenocarcinomas exhibited 8.0-fold and4.5-fold increases (P < 0.01), respectively, in mRNAlevels encoding TR-I_ALK5 andTR-II. In situ hybridization showed that both TR-I_ALK5 mRNAwere highly expressed in the majority of pancreaticcancer cells. Immunohistochemical analysis ofTR-I_ALK5 and TR-II revealedpositive immunostaining in 73% and 56% of the tumors, respectively. Both receptorswere concomitantly present in 54% of the pancreaticcancer samples. The presence ofTR-I_ALK5 or TR-II and theconcomitant presence of TR-I_ALK5 and TR-II in the cancer cells was associatedwith advanced tumor stage (P < 0.01). These findingsshow that in many human pancreatic cancers, increasedlevels of the two signaling TRs are present. The presence of the signaling TRs inadvanced tumor stages indicates a role in diseaseprogression.     

Der Patient als Keimquelle in der Intensivpflegestation

Zusammenfassung 133 Patienten einer Intensivpflegestation, die bei der Aufnahme keine Symptome bakterieller Infektion zeigten und noch keine Antibiotika erhalten hatten, wurden nach dem Zufallsprinzip zwei Gruppen zugeordnet. Eine Gruppe (+Pat.) erhielt eine Antibiotikaprophylaxe mit Penicillinen oder Cephalosporinen, die zweite Gruppe (–Pat.) erhielt keine Antibiotika. Staph. aureus war bei –Pat. im Trachealsekret und in der Umgebung der häufigste potentiell pathogene Keim. Staph. aureus war im Trachealsekret und in der Umgebung der –Pat. signifikant häufiger als bei +Pat.. Klebsiella spp. standen im Trachealsekret und in der Umgebung von +Pat. an erster Stelle. Sie waren im Trachealsekret von +Pat. signifikant häufiger als bei –Pat.. In der ersten Woche des Stationsaufenthaltes traten bei +Pat. starke Veränderungen in der Keimflora der Trachealsekrete auf: die Besiedelung mit gramnegativen Keimen stieg auf fast 100% an, gleichzeitig ging die Frequenz von Staph. aureus zurück. In den Abklatschuntersuchungen aus der Patientenumgebung traten gramnegative Stäbchen bei +Pat. in signifikant höheren Koloniezahlen auf als bei –Pat.. Die paarweisen Vergleiche von Bakterienstämmen aus den Trachealsekreten und aus der Patientenumgebung ergaben, daß +Pat. gramnegative Keime und –Pat. Staph. aureus signifikant häufiger an die Umgebung abgaben. Auf die Kontamination der Patientenumgebung mit Staph. aureus wirkte sich der Faktor der trachealen Intubation nicht aus. Gramnegative Keime waren im Trachealsekret von intubierten Patienten signifikant häufiger als bei nicht intubierten. Derselbe Trend zeigte sich auch in der Patientenumgebung. Die Antibiotikaprophylaxe konnte, wie die klinischen Ergebnisse der Studie zeigten, die Patienten nicht im erwarteten Ausmaß vor Infektionen schützen. Patienten, insbesondere tracheal-intubierte, die Antibiotika erhalten, sind als Streuquellen für hochresistente gramnegative Keime anzusehen.

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The patient as a source of bacteria in intensive care units: Influence of antibiotics and tracheal intubation

Summary 133 patients in an intensive care unit, who prior to admission had not shown any signs of bacterial infection and had not received antibiotic treatment, were assigned to two groups at random. One group received antibiotic prophylaxis with penicillins or cephalosporins (+Pat.), the other group did not receive antibiotics (–Pat.). Staph. aureus was the most frequent facultative pathogen in tracheal secretions and in the environment of –Pat.. This organism was significantly more frequent in –Pat. than in +Pat. in both the tracheal secretions and the enviroment. Klebsiella spp. outnumbered all other species in +Pat.. They were significantly more frequent in tracheal secretions of +Pat. than of –Pat.. In the first week of hospitalisation marked changes were seen in bacterial flora of tracheal secretions of +Pat.. Colonization with gramnegative bacteria rose to nearly 100%, the frequency of Staph. aureus diminishing at the same time. Monitoring by contact cultures revealed that gramnegative rods were significantly more numerous in the environment of +Pat. than of –Pat.. Matching bacterial strains cultured from tracheal secretions and from the environment of the patients proved that +Pat. spread significantly higher numbers of their gramnegative bacteria into the environment. The same is true of –Pat. for Staph. aureus. Intubation had no noticeable effect on the degree of contamination of the surroundings with Staph. aureus. Gramnegative rods were significantly more frequent in tracheal secretions of patients with intubation than in patients without. The same trend was observed for environmental contamination. As the clinical results of this study have shown, antibiotic prophylaxis does not protect patients from infections to the extent expected. Patients, and particularly intubated patients, receiving antibiotic treatment have to be considered as sources of highly resistant gramnegative organisms.

     

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     

Primärer Formwandel der Thrombozyten in vitro

Zusammenfassung Bei der Untersuchung mit dem Interferenz-Kontrast-Mikroskop zeigen die Thrombozyten nach der Blutentnahme im Zitrat-Blut, -Plasma, Heparin- und EDTA-Blut innerhalb von 30–60 charakteristische, quantifizierbare FormverÄnderungen: Quellung, Bildung von Pseudopodien, kleinsten Vesikeln und Unebenheiten an der PlÄttchenoberflÄche. Dieser Formwandel wird durch niedrige Inkubationstemperaturen (4 C, 10 C) gegenüber Zimmer temperatur beschleunigt; bei 37 C lÄuft er verzögert ab. Durch mechanische Alteration bei der Blutentnahme ist eine überproportionale Zunahme von a priori formverÄnderten Thrombozyten im sofort-fixierten Venenblut induzierbar. In vitro ist der Formwandel teilweise, in vivo vollstÄndig oder fast vollstÄndig reversibel. Einige bekannte Aggregationshemmer führen in vitro und z. T. auch nach oraler und intravenöser Applikation zu einer mehr oder minder ausgeprÄgten Hemmung (Bencyclan, SH 869 ASS > D-Propranolol) des Formwandels nach der Blutentnahme. Bencyclan, SH 869 und D-Propranolol bewirken dabei in vitro eine charakteristische Änderung der PlÄttchenform mit Bildung von KugelplÄttchen. Diespontane, primÄre FormverÄnderung der Thrombozyten nach der Blutentnahme ist wahrscheinlich nicht identisch mit der ADP-induzierten (sekundÄren), shape change. Die FormverÄnderung der PlÄttchen beeinflu\t wahrscheinlich das Ergebnis verschiedener Thrombozytenfunktions-und Aggregationsteste. Die Formwandelkinetik von klinisch Gesunden und Hodgkin-Kranken unterscheidet sich signifikant. Es ist möglich, da\ die beschriebene Methode in der Zukunft klinische Bedeutung gewinnt.     

Estrogen receptor beta (ERβ) is expressed in brain astrocytic tumors and declines with dedifferentiation of the neoplasm

Purpose Estrogen receptor (ER) is the second identified receptor mediating the effects of estrogen on target tissues. The role of ER in cancer pathobiology is largely unknown, because specific antibodies have not been available until recently. Initial studies have shown that ER expression declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen receptor (ER) and a pure antagonist of ER, has moderate beneficial effects in human astrocytic neoplasms. However, most published studies agree that glial tumors do not express ER. The purpose of this study was to explore the expression of ER in astrocytic neoplasms.Methods ER expression was monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade I–IV) and in adjacent non-neoplastic brain tissue.Results Moderate or strong nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low-grade astrocytomas, whereas the majority of high-grade tumors were immunonegative or displayed weak immunoreactivity. The progressive decline in ER expression paralleled the increase in tumor grade.Conclusions In as much as ER is possibly the only ER expressed in astrocytes, its decreased expression may play an important role in astrocytic tumor initiation and in the potential response of glial neoplasms to tamoxifen.     

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

Background Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects.Methods A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10mg lafutidine or 20mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364kcal; protein, 10.1g; fat, 16g; carbohydrates, 44.9g; NaCl, 1.1g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored.Results In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole.Conclusions Lafutidine 10mg produces a prompter rise in intragastric pH than rabeprazole 20mg in fasting and postprandial Helicobacter pylori-negative male subjects.     

Uptake and metabolism of radiolabelled GM1-ganglioside in skin fibroblasts from controls and patients with GM1-gangliosidosis

Summary The uptake and metabolism of [3-³H-sphingosine]GM1-ganglioside was measured in cultured skin fibroblasts from controls and patients with infantile, juvenile and adult GM1-gangliosidosis. When dissolved in medium with phosphatidylserine, GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A linear increase in GM1-ganglioside endocytosis was shown with phosphatidylserine concentrations of up to 40m/ml. A pulse-chase study revealed that [³H]GM1-ganglioside was metabolized to GM2-ganglioside, GM3-ganglioside, ceramide dihexoside, ceramide monohexoside, ceramide and sphingosine. Sphingosine was recycled to sphingomyelin. In a 20-h pulse study, cell lines from patients with GM1-gangliosidosis of infantile, juvenile and adult types hydrolysed 2–5%, 20–44% and 54–58% of the total endocytosed GM1-ganglioside respectively. These values were lower than in control cells (64.17 ± 5.43% (n=10)). The hydrolysis rates of exogenous [³H]GM1-ganglioside in cultured fibroblasts from patients with various types of GM1-gangliosidosis closely reflected the clinical severity.Abbreviations GM1 Gal13GalNAc14(NeuAc23)Gal14Galc-1-ceramide - GM2 GalNAc14(NeuAc23)Gal14Glc-1-ceramide - GM3 NeuAc23Gal14Glc-1-ceramide - CDH Gal14Glc-1-ceramide     

Additional value of thallium-201 SPECT to a conventional exercise test for the identification of severe coronary lesions after an episode of unstable coronary artery disease

The additional value of thallium-201 SPECT to a conventional exercise test for the identification of patients with severe coronary lesions was evaluated in 170 men, one month after an episode of unstable coronary artery disease. Severe coronary lesions at coronary angiography — defined as three vessel disease, left main stenosis or proximal left anterior descending artery stenosis as part of two vessel disease — were observed in 45.9%. In the SPECT image, the left ventricular myocardium was divided into nine segments and each segment was classified as either normal (=0), reduced uptake (=1) or uptake defect (=2). The sum of gradings in all segments post-exercise was denoted SPECT score. The patients were divided into nine different groups regarding ST-depression during exercise (no ST-depression, ST-depression in 1–2 leads or 3 leads) and SPECT score (no SPECT score, 1–3 scores or 4 scores). Severe coronary lesions were, in 68% identified by SPECT score 4 and in 65% by ST-depression in 1 lead at exercise test. The specificity for identification of severe coronary lesions was, for both tests, 65%. SPECT score 4 and/or ST-depression in 3 leads identified 82% of the patients with severe coronary lesions with a specificity of 63%. Furthermore, SPECT score 3 identified more patients with isolated proximal left anterior descending artery stenosis than ST-depression alone at exercise test.     

Effects of Piclamilast,a Selective Phosphodiesterase-4 Inhibitor,on Oxidative Burst of Sputum Cells From Mild Asthmatics and Stable COPD Patients

Oxidative stress associated with increased presence of neutrophils is an important feature of inflammatory airways diseases like asthma or chronic obstructive pulmonary disease. We studied the in vitro effect of piclamilast (RP73401), a selective phosphodiesterase (PDE)-4 inhibitor, compared to theophylline and prednisolone, on respiratory burst of sputum cells from mild asthmatics and COPD patients. Sputum cells were harvested from mild asthmatics and stable COPD patients and treated with piclamilast, theophylline or prednisolone. Respiratory burst was assessed by luminol-dependent chemoluminescence after stimulation with 10 M n-formyl-met-leu-phe (FMLP). Piclamilast inhibited FMLP-induced respiratory burst of sputum cells in a concentration-dependent manner (asthma: EC₅₀ approximately 100 nM, max. inhibition: 97.5±5% at 100 M; COPD: EC₅₀ approximately 1 M, max. inhibition: 70.6±4.5% at 100 M), whereas maximal inhibition observed with theophylline (asthma: max. inhib. 27±15%; COPD: 6±2%, both p < 0.05 vs. piclamilast) and prednisolone (asthma: 16±6%; COPD: 7.8±6.2%, both p < 0.05 vs. piclamilast) was weaker. Inhibition by piclamilast was largely reversed through pretreatment of cells with the adenylcyclase inhibitor SQ22536. We concluded that piclamilast, a selective PDE-4 inhibitor, attenuates the respiratory burst of sputum cells from mild asthmatics and COPD patients in vitro. These data underline the potential of PDE-4 inhibition as a novel therapeutic approach to inflammatory airway diseases like asthma or COPD.     

Compound heterozygosity for a β∘-thalassemia (frameshift codons 38/39; -C) and a nondeletional swiss type of HPFH (A→C at NT -110, Gγ) in a Czechoslovakian family

Summary We have analyzed the levels and composition of the fetal hemoglobin (Hb F) in several members of a Czechoslovakian family with a heterozygosity for a newly discovered -thalassemia (codons 38/39; -C), or for a newly detected nondeletional hereditary persistence of fetal hemoglobin (a form of Swiss-HPFH with an AC mutation at nucleotide –100 5 to the Cap site of G), or with a compound heterozygosity for these two conditions. The Hb F level in the -thalassemia heterozygotes averaged 0.3% with low G values ( 28%) and relatively high AT values ( 50%), that in the two Swiss-HPFH heterozygotes averaged 0.8% with 95% G, while that of the compound heterozygote was 3.1% with 95% G. The low Hb F levels were determined with a recently published cation exchange high-performance liquid chromatography (HPLC) procedure that is accurate at the 0.1%–0.2% Hb F level [3]. This method, together with a reversed-phase HPLC procedure, made it possible to detect this unusual type of nondeletional G-HPFH and provided the data indicating that the increased Hb F in the compound heterozygote was derived mainly from the chromosome with the HPFH determinant.This study was supported in part by USPHS Research Grant HLB-41544     

Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine

Histamine H-2 receptors are thought to mediate gastric acid secretory responses, where-as H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mol/kg) into the stomach flap reduced histamine-stimulated (1.25 /kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mol/kg), whereas intravenously administered tripelennamine (40.8 mol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methyl-histamine (2.2 g/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 g/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.     

Untersuchungen mit Phytoagglutininen bei Inzuchthühnern

Zusammenfassung Es wurde in einem Inzuchtstamm von rebhuhnfarbigen Italienern durch drei Generationen der Hi-Faktor mit sechs selbst hergestellten Phytoagglutininen untersucht. Das Vorhandensein des Hi-Antigens konnte bestätigt werden. Seine natürliche Nachweisbarkeit beschränkte sich auf weibliche Tiere. Das vorliegende Gen HI, das dominant vererbt wird, konnte bei beiden Geschlechtern und allen Altersstufen bei Vorhandensein des weiblichen Geschlechtshormons (Östrogen) nachgewiesen werden.

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Summary The Hi-factor was studied with six self-produced phytoagglutinins in an inbred strain of partridge coloured Italiens through three generations. The presence of Hi-antigen could be confirmed. It can only be demonstrated in female animals. The HI gen, which is inherited in a dominant manner, could be demonstrated in both sexes and at all ages in the presence of female sex hormone (estrogen).

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Die Arbeiten wurden mit Mitteln der Deutschen Forschungsgemeinschaft durchgeführt.     

Early and Late QRS Morphology and Width in Biventricular Pacing: Relationship to Lead Site and Electrical Remodeling

48 patients (40 Male), mean age 68 ± 8 years, in III–IV class, with intraventricular conduction delay, received a biventricular pacemaker. Heart failure aetiology was non-ischemic in 60%. Left ventricular lead positioning was inferior in 5 patients (10%), posterior in 12 (25%), lateral in 18 (37%) and anterior in 13 (27%). QRS duration and axis were evaluated in sinus rhythm, and during right ventricular pacing, left ventricular pacing and biventricular pacing, the last early after implant and late after 8.8 ± 4.3 months. QRS duration (ms) was 154 ± 29 in sinus rhythm, 175 ± 28 during right ventricular pacing, 196 ± 31 during left ventricular pacing, 122 ± 23 during biventricular pacing early and 120 ± 18 during biventricular pacing late. All the differences were statistically significant, but not between early and late biventricular pacing. Mean QRS axis (°) was –27 ± 32 in sinus rhythm, –75 ± 4 during right ventricular pacing, 112 ± 41 during left ventricular pacing, –82 ± 51 during biventricular pacing early and –80 ± 42 during biventricular pacing late. Only the difference between left ventricular pacing and all the other groups was statistically significant. QRS axis did not significantly differ according to left ventricular lead site during left and biventricular pacing. Late compared with early biventricular pacing axis showed variation >30° in 35% of patients, in spite of no significant changes in QRS duration and x-ray positioning. Conclusion: Biventricular pacing significantly reduced QRS width, which persisted long-term. Left and biventricular pacing axis was poorly related to left ventricular lead positioning. Biventricular pacing axis variability over time may suggest a role of electrical remodeling.     

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.     

Growth regulation of rabbit gastric epithelial cells and protooncogene expression

We recently developed a primary culture system for gastric epithelial cells from adult rabbits that allows the investigation of growth regulation at the cellular level. In this study, we demonstrated that epidermal growth factor (EGF), insulin, and dibutyryl adenosine 3,5-cyclic monophosphate (dBcAMP) all stimulated cell proliferation. Insulin and dB-cAMP potentiated the stimulation of cell proliferation by EGF, while transforming growth factor-1 (TGF-1) inhibited it. Expression of c-fos and c-myc was induced in response to the stimulation by these growth regulators, but the degree of expression did not necessarily correlate with the effects of these agents on cell proliferation. In conclusion, EGF, insulin, and dBcAMP were positive growth regulators, while TGF-1 was a negative regulator in gastric epithelial cells. These growth modulators may exert their effects by distinct pathways from a standpoint of the expression of c-fos and c-myc.     

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