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.

     

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.     

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the ₃-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the ₂-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1–10 mol/kg) and clenbuterol (0.01–1 mol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1–3 mol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10–100 mol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective –adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a ₃-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mol/kg) nor clenbuterol (100 mol/kg) modified the acid secretion induced by histamine. These data suggest that ₃ adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.     

A deletion of 11 bp (CD 131–134) in exon 3 of the β-globin gene produces the phenotype of inclusion body β-thalassemia

Dominant inherited -thalassemias describe those -thalassemia variants that result in a thalassemia intermediate phenotype in individuals who have inherited only a single copy of the abnormal gene. This form of thalassemia is characterized by moderately severe anemia with jaundice and splenomegaly; it is also characterized by the presence of inclusion bodies in the red blood cell precursors and has, therefore, previously been referred to as inclusion body -thalassemia. We describe a case of inclusion body -thalassemia in a 51-year-old Spanish male caused by a deletion of 11 bp (CD 131–134) in exon 3 of the -globin gene. The deletion of 11 bp in exon 3 of the -globin chain is predicted to produce an anomalous chain of 134 amino acids instead of the normal 146 with an extremely altered amino acid sequence from residues 131–134. Although this shortened variant would lead to a missing H helix, which is involved in ₁₁ contact and ₁₂ subunit interactions, the variant chain can still be bound to the heme group and acquire a secondary structure that is not suitable for the formation of stable dimers or tetramers and also less susceptible to proteolytic degradation. This is the first report of such a -thalassemia mutation.     

Thyroxine induces transition of red towards white muscle in cultured heart cells

Summary Thyroid hormones (TH) have previously been shown to alter the force and velocity of cardiac muscle contractions. To investigate the mechanism responsible for these alterations, excess amounts of thyroxine (T₄, 1M) were applied on rat heart cells grown in cell culture. We found the following biochemical alterations: a) 40% decrease in the myoglobin content within 2 days; b) 25% increase in the rate of Ca-uptake into sacroplasmic reticulum (SR) in myocytes following chemical skinning; and c) a two-fold increase in Na–K-ATPase activity measured by⁸⁶Rb-uptake. These changes support our hypothesis that TH induce the transition of slow-twitch (red) muscles towards the fast-twitch (white) muscle type. This may explain the changes in contractile activity known to occur under TH influence.     

Iron stores in 1359, 30- to 60-year-old Danish women: Evaluation by serum ferritin and hemoglobin

Summary Iron status, including serum (S-)ferritin and hemoglobin (Hb), was assessed in a population survey comprising 1359 nonpregnant Danish women in age cohorts of 30, 40, 50, and 60 years. S-ferritin levels were similar in 30- and 40-year-old women; they displayed a significant increase in 50-year-old women and a further significant increase in 60-year-old women. In the 30- and 40-year-old women, median S-ferritin was 38g/l, 5–95 percentile 6–135g/l; 17.2% had values < 15,g/l (i.e., depleted iron stores), 22.7% values from 15 to 30g/l (i.e., small iron stores), and 60.1% values > 30g/l (i.e., replete iron stores). In the 50-year-old women, median S-ferritin was 54g/l, 5–95 percentile 10–164g/l; 10.3% had values < 15g/l, 16.5% values from 15 to 30g/l, and 73.2% values > 30g/l. For the 60-year-old women, median S-ferritin was 84g/l, 5–95 percentile 25–249g/l; 1.6% had values < 15g/l, 8.6% values from 15 to 30g/l, and 89.8% values > 30g/l. Blood donors (n=180) had lower S-ferritin than nondonors in all age-groups (p<0.001). In the entire series, Hb levels were similar in 30- and 40-year-old women, median 137 g/l (8.5 mmol/l), 5–95 percentile 121–152 g/1 (7.5–9.4 mmol/l), and higher in 50- and 60-year-old women, median 140 g/l (8.7 mmol/l), 5–95 percentile 123-158 g/l (7.6–9.8 mmol/l) (p<0.0001). Hb values < 121 g/l (7.5 mmol/l) were observed in 3.8% of the women. Women with S-ferritin < 15 g/l (n=161) had lower Hb, median 134 g/l (8.3 mmol/l), than those with S-ferritin > 15 g/l, median 139 g/l (8.6 mmol/l) (p<0.001). Iron deficiency anemia (S-ferritin < 15 g/l and Hb < 121 g/l) was seen in 2.3% of 30- and 40-year-old women, and in 1.1% of 50- and 60-year-old women.     

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.     

Local and Systemic Liberation of Proinflammatory Cytokines in Ulcerative Colitis

Determination of plasma and tissue cytokinelevels in inflammatory bowel disease have frequentlyresulted in conflicting data. In the present study wedetermined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokinesinterleukin (IL)-1, IL-6, interferon(IFN)-, and tumor-necrosis factor (TNF)-liberated by peripheral blood mononuclear cells (PBMC)and lamina propria mononuclear cells (LPMC) after 48-hrculture with pokeweed mitogen (PWM). IL-1, IL-6,IFN- and TNF- in the supernatant weredetected by ELISA. Results show low basal levels ofIL-1 secretion by PBMC and LPMC, and a considerableincrease after mitogen stimulation. Basal IL-6production by PBMC was higher in UC patients than incontrols [2029 pg/ml, CI₉ (–165 to4223) vs 572 pg/ml (–383 to 1527) respectively, P = 0.05] and also afterPWM activation [14,995 pg/ml (7759 -22230) vs 6598 pg/ml(3240-9956), respectively, P = 0.05]. In LPMC, nodifferences in IL-6 secretion were observed. TNF- in activated PBMC of patients with UC was notsignificantly increased in relation to control (P =0.09). No constitutive secretion of IFN- wasobserved in mononuclear cells. IFN- levelssecreted by activated LPMC were lower in patients withUC than in controls [1571 pg/ml (–108 to 3251) vs7953 pg/ml (3851-12,055), respectively, P = 0.03]. Theseresults suggest that IL-6, IL-1, and TNF- participate as mediators in the inflammatoryphenomena observed in UC. Further studies are necessaryto evaluate the role of IFN- in thiscondition.     

Thin myofilament proteins in norm and heart failure I. Polymerizability of myocardial Straub actin in acute and chronic heart failure

Summary The reduced and intrinsic viscosities of myocardial Straub F-actin from the left ventricle of a practically healthy man were equal to 3.05±0.2 and 2.4±0.32 and from the right ventricle were 2.37±0.2 and 2.1±0.3 dl/g, respectively (the difference between ventricles was not significant). The average length of filaments measured by flow birefringence technique was equal to 1.3±0.04 m, the number-average length (Ln), determined by the electron microscopy was 1.4 m, the weight-average length (Lw), was 2 m and the maximal one was 5.5 m. The histograms showed that the most characteristic length was that of 0.8–1.2 m.According to the flow birefringence data canine myocardial F-actin had a length similar to that of myocardial F-actin from a practically healthy man, though its reduced and intrinsic viscosities were higher.In acute and especially chronic congestive heart failure the actin polymerizability was sharply reduced. In consequence, in acute heart failure the number-average length of F-actin filaments was decreased by 43% and in congestive heart failure by 65.7%.The characteristic length in acute heart failure shifts to the range of 0.2–0.6 m, while in congestive heart failure the range is 0.2–0.4 m. This fact can possibly explain why during preparation of actin from the pathologically changed myocardium according to the methods including purification by the cycles of polymerization-sedimentation-depolymerization, the pathologically changed actin is discarded and the normal actin remains.A definite parallel was observed between the reduction of actin polymerizability and the ability of myocardial glycerinated fiber bundles (MBGF) to generate force.We conclude that the changes of actin properties in heart failure may cause a decrease in contractibility of the myocardial contractile protein system.     

Comparison of gastric inhibitory polypeptide and intraduodenal or intravenous fat on gastric acid secretion from vagally innervated and denervated canine stomach

Gastric inhibitory polypeptide (GIP), given to dogs in graded doses (range 0.25–2 g/kg/hr) against a constant background stimulation with pentagastrin (4 g/kg/hr), failed to affect the acid secretion at all doses used except the largest one (2 g/kg/hr) which significantly reduced the acid secretion only from the vagally denervated portion of the stomach (Heidenhain pouch, HP) while raising plasma GIP two to three times above the levels reached with duodenal fat. GIP infused in a constant dose (1 g/kg/hr) significantly reduced the HP responses to lower (0.5–2 g/kg/hr) but not to higher (4–16 g/kg/hr) doses of pentagastrin, the kinetics of this inhibition being of competitive type. GIP was ineffective against a constant near maximal stimulation with pentagastrin (4 g/kg/hr), histamine (40 g/kg/hr), or liver extract meal, whereas fat (10 g), given intraduodenally or intravenously, was a powerful inhibitor of acid responses to these stimulants both from the innervated and denervated stomach. Plasma GIP reached similar levels with exogenous GIP and duodenal fat but remained unchanged with intravenous infusion of fat.     

Islet B-cell dysfunction and the time course of recovery following chronic overinsulinisation of normal rats

Summary Appropriate insulin therapy may preserve or improve islet B-cell function whereas the effects of overinsulinisation are unclear. Pancreatic islet B-cell function was therefore studied after overinsulinisation of normal rats for 4 weeks (fed blood glucose 2.2–4.5 mmol/l, controls 4.1–7.0 mmol/l). Insulin secretion was assessed by a 3-h hyperglycaemic clamp (10.0 mmol/l) performed 1, 48, and 120 h after insulin withdrawal (n=6 in each group). When the clamp was performed 1 h after insulin withdrawal, clamp insulin concentration was 1.6±0.1 g/l, compared to 9.3±1.0 g/l in control rats. The integrated area under the plasma insulin concentration curve was also significantly decreased (4.8±0.4 vs 20.3±2.2 g·l^–1·h^–1, p<0.001), but recovered to 9.4±1.0 g·l^–1·h^–1 after 48 h, and to 17.5±1.4 g·l^–1·h^–1 after 120 h. Pancreatic insulin contents were decreased at 1 h (6±1 g/g wet wt) and 48 h (54±12 g/g wet wt) but not at 120 h (221±30 g/g wet wt) after withdrawal (controls, 303±29 /g wet wt) and there was a strong relationship with pancreatic preproinsulin mRNA and the clamp insulin response. Thus, overinsulinisation with prolonged periods of low blood glucose concentrations impairs islet B-cell function, but is reversible over 5 days.     

Changes in expression levels of genes involved in fatty acid metabolism: upregulation of all three members of the PPAR family (α, γ, δ) and the newly described adiponectin receptor 2, but not adiponectin receptor 1 during neonatal cardiac development of the rat

During neonatal cardiac development, the heart changes its substrate preference from glucose to fatty acids. The aim of this study was to investigate the changes in mRNA expression levels of genes involved in the control of cardiac fatty acid metabolism in the transition from neonatal to adult life. Methods mRNA expression levels for peroxisome proliferator activated receptor (PPAR) , and , PPAR co–factor 1 and (PGC–1 and ), 9–cis retinoc–acid–activated receptor , and (RXR , , ), 5–AMP activated protein kinase (AMPK) 1 and 2, adiponectin receptor 1 and 2 (AR 1 and AR 2) were measured in heart tissue of neonatal 0–day, 7–day and 21– day old rats. Results mRNA expression of all three members of the PPAR family were upregulated significantly from day 0 to day 21 ( +117%, +133%, +203%). In addition, m–RNA expression of all RXR isoforms increased from day 0 to day 7 ( +125%, +69%; +41%). AR 2 exhibited a small but significant increase in mRNA expression (+ 46%). Conclusions We were able to demonstrate for the first time that in addition to PPAR, also PPAR and , as well as all RXR isoforms and AR 2 are upregulated in the heart during neonatal development.Drs. Steinmetz and Quentin contributed equally to this publication     

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.     

Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 β chain to recent onset Type 1 (insulin-dependent) diabetes mellitus

Summary A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497–513) AVTPL RIFIVPPAAEY has an 11 amino acid identity with HLA-DQw8 (49–60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496–515) peptide crossreacted with the homologous DQw8 (44–63) peptide but not with the related DQw7(44–63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8(49–60) reacted with the DQw8(44–63) peptide and BOLF1 (496–515), but not with DQw7 (44–63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30;63%) and in sera of 20 non-diabetic control subjects (13 of 20;65%). Sera from diabetic patients did not bind to DQw8 (44–63) or BOLF1(496–515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.     

Reiter’s syndrome following intravesical bacille biliÉ de Calmette–GuÉrin treatment for superficial bladder carcinoma: report of six cases

We report the cases of six patients who developed acute Reiters syndrome following intravesical bacille biliÉ de Calmette–GuÉrin (BCG) immunotherapy for superficial bladder cancer. After the third to eighth BCG intravesical injection, the patients developed conjunctivitis, aseptic urethritis, and polyarthritis consistent with a diagnosis of Reiters syndrome. HLA-B27 antigen was negative in five of the patients examined. Two of the patients responded to nonsteroidal anti-inflammatory drugs for polyarthritis, and the other four responded to steroids (prednisolone 5–10mg/day). The frequent use of intracavitary BCG may increase the incidence of BCG-induced Reiters syndrome. Further analysis of the relationship between HLA-B and -DR alleles and arthritis should shed light on the mechanism of BCG-induced Reiters syndrome.     

β-Adrenoceptor and adenylate cyclase regulation in cardiac myocyte growth

Summary We studied the effect of growth on -adrenergic receptor properties of neonatal rat heart myocytes cultured in serum-free medium with transferrin and insulin. Growth was induced by addition of 1 M (–)-norepinephrine for two days, 200 nM of the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) for two days, or 30 nM T₃ for six days. The K_d values for -receptor binding (¹²⁵I-ICYP) were unaffected by growth. The maximum number of -receptor binding sites calculated as sites/cell was increased 1.47-fold by T₃ (p<.005), but was decreased to 54% of control values by (–)-norepinephrine (p<.005); TPA had no effect on either Kd or B_max values. (–)-Isoproterenol-stimulated adenylate cyclase activity was augmented only in membranes from T₃-treated cells and was reduced by 69% in membranes from (–)-norepinephrine treated cells. TPA had no effect on(–)-isoproterenol-stimulated adenylate cyclase activity. We conclude that the mechanisms controlling -adrenergic receptor number may be distinct from those controlling growth, since receptor number does not correlate with cell enlargement. Furthermore, in (–)-norepinephrine-stimulated growth, which we have shown previously is an ₁-adrenoceptor mediated response, -adrenergic signal transduction is modulated in a directionally opposite fashion.Supported by grants from the Veterans Administration Research Service, American Heart Association California Affiliate, and National Heart, Lung, and Blood Institute Grant HL31113. Dr. Simpson is a Clinical Investigator of the Veterans Administration Research Service.     

Autonomic responses and neurohumoral control in the human early antenatal heart

Summary Previous sporadic findings and the results of recent, more systematic studies now permit us to make an attempt to outline the contribution of the sympathetic and parasympathetic system to the control of the human early antenatal cardiac function. In the developing heart of man, only acetylcholine and catecholamines have so far been proven to act as true autonomic transmitters. Muscariniccholinergic responses to acetylcholine and related agents can be detected from the 4th postconception week onwards, i.e. soon after the initiation of the first heartbeats. The same applies to the -adrenergic responsiveness to noradrenaline, adrenaline and other adrenergic stimulants in a somewhat later period, commencing at week 5 after conception. The maximum cardiac response to all these agonists becomes stronger as development continues. — Evidence is accumulating to suggest that prostaglandins and triiodothyronine might modulate the regulatory function of autonomic transmitters in the human early antenatal heart.Morphological and functional establishment of the autonomic innervation occurs in the human heart well after the appearance of the reactivity to autonomic transmitters. Under in vitro conditions, muscarinic-cholinergic neuro-effector transmission can be demonstrated in 10–12-week-old hearts, and cardiac -adrenergic transmission can first be detected in weeks 13–14. From these observations and from the appearance of the in utero fetal tachycardiac response to atropine in weeks 15–17 and the bradycardiac response to -blockers in weeks 23–28, it seems that the parasympathetic-cholinergic control of the developing human heart becomes functional and can play a role in the overall regulation of the antenatal cardiac function carlier than the sympathetic-adrenergic neural control. In the period before the onset of sympathetic neural control, the adrenergic regulation of the antenatal heart is achieved predominantly through the extra-adrenal (mainly the para-aortic) chromaffin tissues, whereas the co-operative function of the adrenal medulla becomes effective later in fetal life.     

Characteristics of lysosomal phosphomannosyl-enzyme receptors in the rat heart

Summary The receptor system recognizing mannose 6-phosphate groups of lysosomal enzymes has been characterized, e. g. in fibroblasts and liver cells. The purpose of this study was to demonstrate the presence of a phosphomannosyl receptor system in rat heart muscle. The characterization of receptors was accomplished with -N-acetylglucosaminidase (-GA) secreted by rat embryo fibroblasts after ammonium chloride stimulation. The receptor binding of ligand enzymes was saturated by adding increasing concentrations of -GA and the binding increased linearly when the content of membrane protein was increased. The binding of -GA was inhibited by mannose and glucose phosphates, especially mannose 6-phosphate. Mannose itself did not inhibit binding of the enzyme, showing that the binding was not mediated by mannose receptors. Alkaline phosphatase treatment of -GA decreased the binding of ligand enzymes to receptors. Alkaline conditions increased the dissociation of receptorligand complexes, whereas the dissociation was minimal between pH 5.5 and 6.5. The proportion of endogenous -GA activity in membranes probably representing receptor-bound location, varied between 40 and 55% of the total activity in various parts of rat cardiac muscle. The differences in the content of phosphomannosyl receptors, however, were insignificant between various cardiac muscle samples. At the organelle level the highest specific binding capacity, as well as the highest endogenous ß-GA activity, was in the sarcolemmal fraction. These results suggest that phosphomannosyl receptors also function in the endocytosis and transport of lysosomal enzymes in cardiomyocytes, as well as in several other cell types studied.     

The Physical Conditions of Different Organs Are Reflected Specifically in the Pressure Pulse Spectrum of the Peripheral Artery

We try to solve the hemodynamic inverse problem of the internal organs in terms of the peripheral pressure pulse spectrum analysis. Side-branch organs are approximated as resonators with own natural frequencies. They are depicted not as ordinary reflection sites but as antennas that receive energy from the main artery and undergo forced oscillations with selective frequencies. Every organ also reacts back to the main artery as a secondary small heart source that generated harmonic forces with maximum amplitude near its own natural frequency. The whole arterial system is in a steady distributed oscillatory state that is the superposition result of encountering the forces generated by the heart and many internal organs. A frequency matching theory of the organ and the main artery is proposed. The Fourier components of the pressure pulse in the arterial system are related to the matching conditions of different organs. In vivo studies in kidney and spleen of rats are provided.     

Intracytoplasmatische Glykogenablagerungen,lamelläre Strukturen und virus-ähnliche Einschlüsse in Mastzellentumoren des Hundes. Eine elektronenmikroskopische Untersuchung

Zusammenfassung Gefunden wurden: Bis zu 6 große Einschlüsse, welche aus Glykogenkörnchen bestehen; rundliche, bis zu 1,5 große, aus Lamellen zusammengesetzte Strukturen; virusähnliche Partikel (30–32 m), die einzeln oder zu mehreren in membranumgebenen Haufen liegen.

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Intracytoplasmatic glycogen deposits, lamellate structures and virus-like inclusions in mast-cell tumours of dogs. An electron-microscopic study

Summary The following were encountered: inclusions measuring up to 6 and composed of glycogen grains; round structures measuring up to 1.5 , and consisting of laminae; viruslike particles (30–32 m) either occurring as single bodies or accumulations. The latter were surrounded by a single membrane.