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.     

Effect of insulin on glucagon enhanced lipolysis in vitro

Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these physiological concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100U/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.This work was supported by the Fonds National de la Recherche Scientifique and the Fonds de la Recherche Scientifique Médicale, Belgium.     

Ultrastructural changes in A-cells exposed to diabetic hyperglycaemia. Observations made on pancreas of chinese hamsters

Summary Pancreatic A-cells of chinese hamsters with diabetes of varying severity and duration were examined by electron microscopy. Two predominant changes were observed: 1. Lysosomal digestion of secretory granules (granulolysis, crinophagy) occurred in practically all A-cells of diabetic animals but was rarely observed in those of normoglycemic controls. This is considered a response of A-cells to the cessation of glucagon release secondary to hyperglycemia. 2. In relatively degranulated A-cells of ketotic diabetic animals, dilatation of the cisternae of the RER was seen together with accumulation of pale, flocculent material, possibly reflecting persisting or enhanced glucagon synthesis. In addition, numerous maturing secretory granules were seen in the cisternae of the Golgi complex. Since these apparently contradictory phenomena may be seen in the same cell, it is suggested that granulolysis may not only result from decreased hormone release secondary to hyperglycemia but that different and independent stimulatory signals may exist for glucagon synthesis, for glucagon release, and for the initiation of granulolysis.Supported in part by the Fonds national suisse de la Recherche scientifique (Grants. No. 4848.3 and 3.154.69).     

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.     

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.     

Association of polymorphism in the interferon γ gene with IDDM

Summary Cytokines may play importmant roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon (IFN-) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p=0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p=0.006) or in the young-onset (<10 years) patients (p=0.0006). The alleles 3 and 6 were increased in the IDDM patients, and a significant increase in the frequency of the 3/6 genotype was observed in the IDDM patient group (9.1%, RR 2.9, p=0.010), in the patients with initial insulin therapy less than 1 year from onset (10.6%, RR 3.4, p=0.004), or in the young-onset patients (16.7%, RR 5.7, p=0.0003) in comparison to the control subjects (3.4%). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with 3/6 or 6/6 in comparison to the patients with other genotypes. These results suggest that the IFN- gene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - HLA human leucocyte antigen - IFN- interferon - NIDDM non-insulin-dependent diabetes mellitus - PCR polymerase chain reaction - ICA islet cell antibody - TNF- tumour necrosis factor - IL-1 interleukin-1 - INS insulin gene     

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.

     

Extraction,gel filtration pattern,and receptor binding of porcine gastrointestinal glucagon-like immunoreactivity

Summary Different techniques for the extraction and initial purification of porcine gastrointestinal glucagon-like immunoreactivity (GLI) were compared with reference to yield, and preservation of number and pattern of GLI components. The conventional acid-ethanol technique combined with ethanol-ether purification gave high yields and a reproducible pattern of components. Large amounts of tissue were more easily extracted using another technique, based on extraction by boiling, extraction and precipitation with acetone, and — if necessary — salting out. — By means of the latter two techniques mucosal tissue from all of the porcine gastrointestinal tract was extracted and subjected to gel filtration. Glucagon-like peptides were searched for using: — 1. a radioimmunoassay which quantifies gut type glucagon (GTG), as well as pancreatic type glucagon (PTG), 2. a radioimmunoassay highly specific for pancreatic type glucagon (PTG), and 3. a radioreceptor assay based on binding of glucagon to porcine liver cell membranes. — The oesophageal, the fundic, and the antro-pyloric parts of the gastric mucosa contained very small amounts of GLI. The cardiac gland region contained small amounts of a peptide indistinguishable from true glucagon. The duodenal mucosa contained small amounts of true glucagon and may be a smaller, glucagon-like peptide. The mucosa of the small intestine contained large amounts of both high and low molecular weight GTG and, in addition, PTG of high molecular weight and true glucagon. The colon also contained these components with true glucagon in high concentrations. Only small GTG and true glucagon were receptor-active, the former with less than its immunometric potency.     

Endocarditis caused by Gemella haemolysans

Summary Gemella haemolysans, a coccus related to theStreptococcaceae, was isolated from the blood of a patient with endocarditis. The patient was successfully treated with a combination of penicillin G and tobramycin, followed by clindamycin. The taxonomy of this organism, especially its relationship toStreptococcus morbillorum is discussed and previously reported cases ofGemella infections are reviewed.

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Endokarditis durch Gemella haemolysans

Zusammenfassung Aus Blutkulturen einer Patientin mit einer Endokarditis wurde einGemella haemolysans-Stamm angezüchtet, ein zu denStreptococcaceae gehöriges Bakterium. Die Patientin konnte mit einer Kombination von Penicillin G und Tobramycin sowie anschließender Clindamycin-Therapie erfolgreich behandelt werden. Die Taxonomie des Erregers, insbesondere seine Verwandtschaft zuStreptococcus morbillorum, wird diskutiert und eine Übersicht über kürzlich beschriebeneGemella-Infektionen gegeben.

     

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.     

Insulin and growth hormone responses to glucose loading in treated acromegalics

Summary The insulin and growth hormone responses to oral glucose load (100 g) in 23 acronaegalic patients, previously treated by external irradiation, are described. Based on current clinical findings, sixteen acromegalics were considered inactive and seven patients active. Two of the latter were treated diabetics. Thirteen healthy, non-obese subjects formed the control group. Five inactive acromegalics had blood glucose values exceeding the upper limits of normal after the glucose load. Both the inactive and active acromegalics had hyperinsulinemia in the fasting state and after glucose load. The observation of an exaggerated serum insulin response to glucose load in clinically inactive acromegalics suggested that chronically elevated levels of circulating growth hormone may have led to permanent changes in the responsiveness of the pancreatic islets to glucose stimulation. The mean fasting value of serum growth hormone was about the same in the controls and the inactive acromegalics; the latter did not show suppression in serum growth hormone levels after glucose load.Research Fellow, Medical Research Council of Canada     

Dosis-Wirkungs-Beziehungen bei der Erzeugung von Hämangioendotheliomen der Leber bei Mäusen durch Diäthylnitrosamin

Zusammenfassung Quantitative Fütterungsversuche bei Mäusen des DBA-Stammes mit Diäthyl-nitrosamin ergaben, daß bei Verkleinerung der Tagesdosis auch die zur Erzeugung von Hämangioendotheliomen der Leber benötigte Gesamtdosis kleiner wird. Die Krebserzeugung verläuft auch bei Mäusen nach der allgemeinen Formel d · t ⁿ=konst. als beschleunigter Vorgang nach Art einer Verstärkerwirkung.

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Summary Quantitative feeding experiments in mice of the DBA strain with di-ethyl-nitrosamine disclosed that with a reduction of the daily dose the total dosage needed for the induction of hepatic hemangioendotheliomata also became smaller. The induction of cancer in mice occurs according to the general formula d · t ⁿ=K, as an accelerated process much like an intensifier action.

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Mit 1 Textabbildung

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Die Arbeit wurde durch die Deutsche Forschungsgemeinschaft unterstützt.     

Heterogeneous glycaemic and insulinaemic responses to oral glucose in non-diabetic men: interactions between duration of obesity,body fat distribution and family history of diabetes mellitus

Summary The interaction between environmental and genetic factors in the alterations of glucose-insulin homeostasis was studied in 104 non-diabetic men. Family history of diabetes mellitus was used as an index of genetic predisposition to diabetes. Body composition was measured by under-water weighing whereas subcutaneous and visceral adipose tissue areas were measured at the abdominal and femoral levels by computed tomography. The sample was first divided into two groups. The first group included subjects with normal glycaemic and insulinaemic responses during a 75 g oral glucose tolerance test. The second group was composed of subjects either with a high glucose response or high insulin response or both. Men included in the second group were different from the normal subjects for almost all body fatness variables. They also presented a prevalence of a positive family history of diabetes which was significantly higher than normal subjects. The second group was then divided into three distinct subgroups based on insulin and glucose responses of the subjects during the oral glucose tolerance test. Subjects with high insulin but normal glucose responses were characterized by significantly higher levels of total body fat and deep abdominal adipose tissue when compared to the normal group (p<0.05). Men with both high insulinaemic and glycaemic responses displayed higher body fatness values and higher deep and subcutaneous abdominal adipose tissue areas (p<0.05) in comparison with normal subjects. They also had a higher body mass index at age 20 years than control subjects and subjects with high insulin but normal glucose responses. In contrast, subjects with normal insulin but with high glucose responses were not different from the normal group with regard to body fat and adipose tissue areas. These results show the heterogeneous origin of altered glucose-insulin homeostasis in non-diabetic men. Finally, subjects in the altered glucose-insulin homeostasis group with no family history of diabetes displayed a higher body mass index at age 20 years (p<0.05) in comparison with subjects who had a positive family history of the disease. They also presented a greater abdominal-to-thigh fat ratio measured by computed tomography. These results suggest that in men with alterations of glucose-insulin homeostasis, the relationship of body fat distribution to glucose tolerance and plasma insulin levels is different in those with no family history of diabetes than in subjects with a positive family history of diabetes.     

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     

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.     

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     

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.

     

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.     

Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in Type 1 diabetic patients

Aims/hypothesis Altered glucose transporter expression has been implicated in the pathogenesis of diabetic nephropathy. There is increasing evidence that genetic factors convey risk of, or protection from, diabetic nephropathy and that the behaviour of cultured skin fibroblasts from Type 1 diabetic patients may reflect these genetic influences. This study aimed to compare GLUT1 mRNA expression levels in skin fibroblasts from Type 1 diabetic patients with either rapid (fast-track, n=25) or slow (slow-track, n=25) development of diabetic nephropathy and from non-diabetic normal control subjects (controls, n=25).Methods Skin fibroblasts were cultured in Dulbeccos Modified Eagles Medium with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels were estimated by microarray analysis and RT-PCR.Results Levels of GLUT1 mRNA expression in skin fibroblasts from slow-track patients were greater than those from fast-track patients (p=0.02), as initially detected by microarray. GLUT1 mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts from slow-track patients (4.59±2.04) than in those from fast-track patients (3.34±1.2, p=0.02), and were also higher than in skin fibroblasts from control subjects (3.52±1.66, p=0.03). There was no statistically significant difference between levels of expression in the fast-track patients and the control subjects.Conclusions/interpretation This finding is consistent with the presence of cellular protection factors against diabetic nephropathy in the slow-track patients. These factors could be associated with the regulation of the GLUT1 pathway and may be genetically determined.     

Different meals produce different digestive motility patterns

The purpose of these experiments was to characterize the pattern of digestive myoelectric activity produced by four different test meals in dogs. A new approach for the analysis of the myoelectric activity of the small intestine was used. In contrast with methods dividing the tracings into present time periods, the present method respected the motor entities, hence the continuity, of the tracing. Two types of motor entities occurred: activity units which are groups of consecutive slow waves with spiking, and rest units, which are groups of consecutive slow waves without spiking. The frequency of occurrence and frequency of alternation of the various activity and rest units occurring during digestion was calculated. Digestive myoelectrical activity was characterized by the frequent occurrence and alternation of short activity and rest units. Three different patterns of digestive activity could be discriminated, ie, a fat, a protein and carbohydrate, and a canned food pattern.