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.     

Diagnosis of the mucopolysaccharidoses using cultured skin fibroblasts and amniotic fluid cells

Assay of-L-iduronidase, heparin sulphamidase,N-acetyl--D-glucosaminidase, arylsulphatase B,-L-fucosidase,-glucuronidase,-galactosidase and-D-mannosidase in cultured cells is described. Activities in deficient fibroblast strains are compared to control fibroblast strains. The first case of Sanfilippo B in the United Kingdom is reported. A comparison of enzyme activities in cultured fibroblasts and amniotic fluid cells is made.     

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     

Typing of intermediate filaments in malignant fibrous pleural tumors

Summary We report two cases of a malignant fibrous pleural tumor, one of the localized type and one of the diffuse type. In both cases, typing of intermediate filaments by immunofluorescence microscopy showed that the tumor cells were positive for vimentin and negative for (cyto)keratin and desmin. This result supports the concept that malignant fibrous pleural tumors do not arise from the (cyto)keratin-positive pleural mesothelium but from the submesothelial fibrous tissue. Thus, instead of the usual term malignant fibrous mesothelioma, the term malignant submesothelial fibrosarcoma should be preferred.     

Zur Rolle der enzymatischen DNA-Reparatur bei Carcinogenese und Krebschemotherapie

Ohne ZusammenfassungCancer Research and Clinical Oncology publishes in loose succession Editorials and Guest Editorials on actual and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author. The EditorsDie Zeitschrift für Krebsforschung und Klinische Onkologie bringt in zwangloser Folge Editorials zu aktuellen und/oder kontroversen Problemen der experimentellen und klinischen Onkologie. Diese Beiträge geben ausschließlich die persönliche Meinung des Autos wieder. Die HerausgeberHerrn Prof. Harold P. Rusch, Madison, Wisc., in aufrichtiger Verehrung zum 70. Geburtstag gewidmet     

Human Plasma Fibronectin Mediates Adhesion of U937 Cells by RGD and CS1

Fibronectin specifically binds to U937 cells (monocytic cell line) in a dose-dependent manner. The specific receptors for the RGD sequence have been identified as ₅₁ and _IIb3, and that for CS1 has been defined as ₄₁. RGDS, CS1 peptide, and two peptides together showed similar inhibitory activities on this adhesion, while the 29-kD dispase-digested fragment of the C-terminal heparin-binding domain did not. Thus, the adhesion of fibronectin to U937 cells is mainly mediated by RGDS in the cell-binding domain and CS1 in the alternatively spliced region. Flow cytometry using monoclonal antibodies revealed expressions of ₃₁, ₄₁, and ₅₁, and not expression of ₂₁. Adhesion of U937 cells to fibronectin-coated wells is specific and is inhibited by anti-₄₁ and anti- ₅₁ monoclonal antibodies. The IC-50 for anti-₅₁ antibody was almost a log lower than the value for anti-₄₁ antibody. These results demonstrated that interactions of RGDS and CS1 sequence of fibronectin with ₅₁ and ₄₁ on U937 cells were required for the adhesion of U937 cells to fibronectin. These results may provide further information to understand the mechanism(s) of tumor cell adhesion and atherogenesis.     

Increased levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in tracheal aspirates of newborns with pneumonia

Summary Pneumonia is one of the major sites of infection in ventilated newborns. We investigated whether the cytokines IL-1 and TNF- are detectable in tracheal aspirates of newborns with pneumonia as a diagnostic marker. All 12 infants with pneumonia had elevated levels of IL-1 (range 30–300 pg/ml) and TNF- (range 60–680 pg/ml), whereas control infants (n=21; respiratory distress syndrome, very low birth weight or infants intubated preoperatively) had no detectable levels of IL-1 or TNF-.In vitro investigations with mononuclear cells of umbilical cord blood were performed to rule out that exogenously added surfactant influences IL-1 and TNF- production. It is concluded that IL-1 and TNF- are important and specific mediators of neonatal pneumonia which may be of diagnostic importance.

---

Erhöhte Spiegel von TNF- und IL-1 im Trachealsekret von Neugeborenen mit Pneumonie

Zusammenfassung Die Pneumonie ist eine der Hauptlokalisationen von Infektionen bei Neugeborenen. Wir untersuchten, inwieweit die Zytokine IL-1 und TNF- im Trachealsekret von Neugeborenen mit Pneumonie als diagnostischer Marker nachgewiesen werden können. Alle 12 Kinder mit Pneumonie hatten erhöhte Spiegel für IL-1 (30–300 pg/ml) und TNF- (60–680 pg/ml), während die Kontrollen (n=21; Atemnotsyndrom, sehr untergewichtige Neugeborene, präoperativ intubierte Kinder) keine nachweisbaren Spiegel für IL-1 und TNF- hatten. Um auszuschließen, daß exogen appliziertes Surfactant die IL-1 und TNF--Produktion beeinflußt, wurdenIn vitro-Untersuchungen mit mononukleären Zellen von Nabelschnurblut durchgeführt. Wir schließen aus den Ergebnissen, daß IL-1 und TNF- wichtige und spezifische Mediatoren der Neugeborenenpneumonie sind, die von diagnostischer Bedeutung sein können.

     

Macrophages enhance binding of beta-VLDL and cholesterol ester accumulation in cultured aortic smooth muscle cells

Summary The effect of macrophages on the uptake of -very low-density lipoprotein (-VLDL) by smooth muscle cells (SMC) expressing different morphological phenotypes was examined in culture. The SMC were grown alone and in co-culture with macrophages for four days, then incubated with different concentrations of¹²⁵I--VLDL for 3 h at 4°C or with 75 ug/ml -VLDL for 24h at 37°C. The binding of -VLDL to SMC at 4°C was enhanced in the presence of macrophages irrespective of the phenotype expressed by SMC. This occurred through modification of the lipoprotein, since binding of re-isolated macrophage-conditioned -VLDL to SMC was 12.5 times that of fresh -VLDL. This modified form of -VLDL competed with fresh -VLDL for binding to SMC. Binding was inhibited in the presence of probucol, suggesting that an oxidative mechanism may be involved.The presence of macrophages also enhanced the accumulation of -VLDL-derived cholesterol in SMC. While most of this is a consequence of the enhanced binding, macrophages may also act directly on SMC to increase cholesterol accumulation, since the activity of acid cholesterol ester hydrolase and neutral cholesterol ester hydrolase in SMC was reduced in the presence of macrophages.     

17β-Estradiol Attenuates Quinolinic Acid Insult in the Rat Hippocampus

A number of studies have shown that 17-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17-estradiol against quinolinic-acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 mol quinolinic acid in 2 L phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM–5 M 17-estradiol or quinolinic acid. The results show that 17-estradiol protects hippocampal neurons from quinolinic-acid-induced neurodegeneration by competing with quinolinic acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.     

Local and regional immunotherapy of cancer with interleukin 2

Conclusion The results obtained in preclinical systems as well as the first clinical trials suggest that local IL-2 immunotherapy may represent a novel approach to the treatment of some neoplasms. However, the experimental results should be confirmed and substantially extended before definitive conclusions can be drawn. We hope that the data and considerations discussed in this article will facilitate thoughts concerned with future clinical IL-2 trials and be instrumental in the optimization of IL-2 cancer immunotherapy.The Journal of Cancer Research and Clinical Oncology publishes in loose succession Editorials and Guest editorials on current and/or controversial problems in experimental and clinical oncology. These contributions represent exclusively the personal opinion of the author     

A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 m thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08±1.10 m, 3.95±1.02 m, 5.04±1.56 m, and 6.11±2.23 m, the circumferences of those vessels seen as complete circles were 43.11±12.78 m, 43.71±12.87 m, 95.21±39.32 m, and 126.77±54.65 m; the lengths between vessel bifurcations were 13.28±3.08 m, 13.47±4.58 m, 24.91±9.66 m, and 41.82±28.08 m in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.     

Inborn errors of bile acid metabolism

Summary Cholesterol is converted to cholic acid and chenodeoxycholic acid by a series of reactions involving modifications to the steroid nucleus and oxidation of the side chain. These reactions can be affected by a number of inborn errors of metabolism. When this happens unusual bile acids or bile alcohols are synthesized; these can be identified using gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry techniques. Two defects affecting the modifications to the steroid nucleus have been described; both present with cholestatic liver disease of neonatal onset. The better characterized of the two — 3-hydroxy-5-C27-steroid dehydrogenase deficiency — leads to excretion of 3-7-dihydroxy-5-cholenoic acid and 3,7,12-trihydroxy-5-cholenoic acid in the urine. The liver disease improves dramatically on treatment with chenodeoxycholic acid. Deficient activity of 3-oxo-4-steroid 5-reductase is thought to be the cause of familial liver disease in some infants who excrete 7-hydroxy-3-oxo-4-cholenoic acid and 7,12-dihydroxy-3-oxo-4-cholenoic acid in the urine. However, diagnosis of this disorder is problematical; a similar pattern of metabolite excretion can occur as a result of liver damage caused by viruses or inborn errors of pathways unrelated to bile acid synthesis. Defective side chain oxidation in patients with cerebrotendinous xanthomatosis (CTX) leads to synthesis of bile alcohols such as 5-cholestane-3,7,12,25-tetrol and 5-cholestane-3,7,12,23,25-pentol. Patients with CTX do not have cholestatic liver disease. Their major problems (neurological disease, atherosclerosis and xanthomata) are caused by accumulation of cholestanol and cholesterol in the tissues. Bile acid precursors are probably diverted into synthesis of cholestanol. Chenodeoxycholic acid suppresses the production of abnormal metabolites from cholesterol (by inhibition of cholesterol 7-hydroxylase) and leads to improvement in the neurological disease. Defective side chain oxidation also occurs in peroxisomal disorders but this time it leads to accumulation of C27 bile acids such as 3,7,12-trihydroxy-5-cholestanoic acid (trihydroxycoprostanic acid, THCA). This compound is readily detected in the bile and plasma of patients with defects of peroxisome biogenesis. In patients with defects of a single peroxisomal-oxidation enzyme (the 3-hydroxyacyl-CoA component of the bifunctional protein or the thiolase), the major C27 bile acid in bile may be 3,7,12,24-tetrahydroxy-5-cholestanoic acid (varanic acid). In addition to the above inborn errors, others which are less well characterized undoubtedly exist, as do defects of bile acid transport across membranes.     

Adult “idiopathic” extrahepatic venous thrombosis

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a latent myeloproliferative disorder has been reported in adults with idiopathic EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The idiopathic group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17–70) with a median follow up of 96 months (19–372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.Supported by R Farini Foundation for Gastroenterology Research.     

Structural basis of the developmental plasticity in the human cerebral cortex: The role of the transient subplate zone

We correlated neuroanatomical developmental parameters with sequential ultrasonography scans to reveal the structural basis of functional recovery after early focal hypoxic lesions of the human frontal lobe in premature infants. We studied the transient fetal subplate zone in the premotor and prefrontal cortex in premature, newborn, infant, and young adult brains by acetylcholinesterase (AChE) histochemical, Golgi, and immunocytochemical methods. The structuralin vivo rearrangements of the cerebral wall after perinatal lesions were studied on serial real-time sector scans (5-MHz transducer). The subplate zone contains waiting axons and randomly oriented fetal neurons, its developmental peak is between 22 and 34 weeks of gestation, and it is present in the frontal cortex of newborns and disappears after the sixth postnatal month, but individual subplate-like neurons remain until adulthood. Ultrasonography revealed remarkable structural rearrangements of the cerebral wall when the hypoxic lesion occurred during the developmental peak of the subplate zone: anechoic cavities (cysts) develop rapidly (within 3 weeks) in premature brains, the rebuilding of these lesions continues after birth, and cavities disappear around the 11th month. We propose that the transient population of waiting axons and cells of the subplate zone participate in the structural and functional plasticity of the human cerebral cortex after perinatal brain damage.     

Enzyme Pattern of Macrophages in the Course of Inflammation

Zusammenfassung Die Zytologie der akuten Entzündung wurde mittels der modifizierten Hautfenster-Methode untersucht. Das Vorliegen eines ständigen Anstieges der Aktivität der Enzyme: saure Phosphatase und Succinat-Dehydrogenase sowie DPNH-Diaphorase bei Entzündungsmakrophagen wurde beobachtet.

---

Summary Cytology of acute inflammation was followed by means of modified skin window method. Cytochemical evidence of continuous increase of activity of the enzymes acid phosphatase, succinic dehydrogenase and DPNH diaphorase in inflammatory macrophages was observed.

     

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n=7; E-LAVAGE, n=5) or bolus (I-BOLUS, n=8; E-BOLUS, n=5), or went untreated (CONTROL, n=4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO₂ were observed in the lavage groups compared to the bolus groups and the controls. PaO₂ (mmHg) at 240 min posttreatment: I-LAVAGE=297±54, E-LAVAGE= 280±57; I-BOLUS=139±31; E-BOLUS=152±29; C=119±73 (mean± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.     

Gene expression of cytokines suppressing hematopoietic progenitor cells in lymphoid malignancies

Summary The expression of cytokine genes for tumor necrosis factor (TNF), lymphotoxin and transforming growth factor (TGF), all of which are known to suppress normal hematopoiesis, was investigated in 32 patients with lymphoid malignancies using Northern blot analysis. Messenger RNA (mRNA) for TNF, lymphotoxin and TGF was detected in 9 cases, 2 cases and 7 cases, respectively. When the relationship between cytokine gene expression and surface phenotype was analyzed, the expression of CD19 correlated significantly with expression of the TNF gene (P<0.05). This suggests that B cell malignancies are likely to produce TNF. When the hematological parameters of patients expressing and not expressing the gene were compared, the expression of TNF mRNA was found to correlate with more profound anemia in acute lymphoblastic leukemia (P<0.05). Both granulocyte and platelet counts were lower in patients expressing TNF mRNA; however, the decreases were not significant. Neither lymphotoxin nor TGF gene expression correlated significantly with any hematological parameter.Abbreviations TNF tumor necrosis factor - TGF transforming growth factor - IL interleukin - ALL acute lymphoblastic leukemia - CLL chronic lymphocytic leukemia - ATLL adult T-cell leukemia/lymphoma - NHL non-Hodgkin's lymphoma - MM multiple myeloma Partly supported by grants-in-aid from the Ministry of Education, Science and Culture of Japan (60770949, 63015063, 02256102, 03670325) and from the Fukuoka Anti-Cancer-Society.     

Secretory component and lactoferrin in pure pancreatic juice in chronic pancreatitis

To evaluate pathophysiological roles of proteins in pancreatic secretion, immunoreactive lactoferrin (LF) and secretory component (SC) were measured in the first fraction of the pure pancreatic juice obtained endoscopically from 17 control, 21 suspected (SCP), 14 noncalcified (NCP), and 14 calcified chronic pancreatitis (CCP) subjects. The protein and amylase tended to decrease both in concentration and output from control to CCP. LF concentration was elevated in CCP (18.0±4.9/ml) when compared with controls (2.3±0.2g/ml), and LF output in NCP (12.3±3.8 g/min) was increased from controls (3.8±0.6 g/min). The combination of high LF concentration with low protein output was observed in 10/14 in CCP but 0/14 in NCP and can be a biochemical discriminator of CCP from NCP. SC concentrations were also elevated in NCP (8.5±2.0 g/ml) and CCP (5.6±1.6 g/ml) from controls (1.2±0.2 g/ml). SC outputs in SCP (9.8±3.1 g/min) and NCP (21.1±4.8 g/min) were increased from controls (1.7±0.3 g/min), but there was no further increase in CCP. Hypersecretion of LF and SC in chronic pancreatitis is different, especially in CCP, although the mechanisms for hypersecretion are unknown.This study was supported in part by a research grant for intractable pancreatic disease from the Ministry of Health and Welfare, Japan.     

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.     

Interpretation of blood cultures yielding staphylococcus aureus

Summary Forty-eight patients with blood cultures positive for Staphylococcus aureus were classified according to clinical criteria in three groups: definite, possible, and doubtful septicemia. Using traditional blood culture sets with two bottles (thioglycollate and tryptic soy broths), we found that patients with definite septicemia always showed more than one positive bottle per day if more than one set was drawn, that the mean detection time was 1.7 days, and that 95% of the first positive bottles and 92% of all positive bottles grew within two days of incubation. Patients with doubtful septicemia were more often (88%) positive in one bottle only, the mean detection time for all bottles was 3.7 days, and only 35% of the first positive bottles and 33% of all positive bottles yielded growth within two days. Possible cases took a position between these two extremes but tended more towards the doubtful cases. The implications of these findings for the interpretation of blood cultures with S. aureus are discussed.

---

Interpretation von Blutkulturen mit Staphylococcus aureus

Zusammenfassung 48 Patienten, aus deren Blutkulturen Staphylococcus aureus gezüchtet worden war, wurden nach klinischen Kriterien in drei Gruppen eingeteilt: unzweifelhafte, mögliche und zweifelhafte Septikämie. Bei Verwendung eines traditionellen Blutkultursystems mit zwei Flaschen pro Kultur (Thioglykolat- und Tryptic Soy-Bouillons) ergab sich, daß Patienten mit unzweifelhafter Septikämie stets mehr als eine positive Flasche pro Tag aufwiesen — sofern mehr als eine Kultur pro Tag entnommen worden war —, daß die mittlere Bebrütungsdauer bis zur Positivität 1,7 Tage betrug, und daß 95% der ersten positiven Flaschen und 92% aller positiven Flaschen innerhalb von zwei Tagen Wachstum von S. aureus zeigten. Patienten mit zweifelhafter Septikämie zeigten häufiger (in 88%) Wachstum in nur einer Flasche, die mittlere Bebrütungsdauer betrug 3,7 Tage, und nur 35% der ersten positiven Flaschen und 33% aller positiven Flaschen ergaben Wachstum innerhalb von zwei Tagen. Mögliche Septikämien nahmen eine Zwischenstellung ein, tendierten jedoch mehr nach der zweifelhaften Kategoric. Folgerungen für die Interpretation von Blutkulturen mit S. aureus werden diskutiert.