Glycerin und freie Fettsäuren im Blutplasma bei hypotrophen Neugeborenen

Zusammenfassung Bei 10 hypotrophen Neugeborenen (Geburtsgewicht unter 2500 g bei normaler Schwangerschaftsdauer) wurden während der ersten 2 Lebenstage Glycerin, freie Fettsäuren und Glucose im Plasma bzw. Vollblut bestimmt. Glycerin und freie Fettsäuren steigen unmittelbar nach der Geburt an. Dabei ist der Glycerinanstieg höher als bei Frühgeborenen mit vergleichbarem Geburtsgewicht. Der Anstieg freier Fettsäuren ist nicht so ausgeprägt. Es ließ sich feststellen, daß bei niedriger Körpertemperatur der Fettsäurespiegel in den ersten Stunden nach der Geburt niedrig ist, bei normaler Körpertemperatur die Fettsäurewerte erhöht sind. Wesentliche Veränderungen des Blutglucosespiegels ließen sich nicht nachweisen. Bereits die Ausgangswerte sind bei hypotrophen Kindern niedrig.Die Elimination von intravenös zugeführtem Glycerin wurde bestimmt. Gegenüber Frühgeborenen und normalgewichtigen Neugeborenen ist die Glycerinelimination beschleunigt. Daraus kann man auf eine vermehrte Utilisation schließen. Es wird diskutiert, inwieweit endogen entstehendes Glycerin (aus der Hydrolyse der Triglyceride) im Stoffwechsel hypotropher Kinder direkt zur Energiegewinnung herangezogen wird. Gerade die energetische Versorgung des Gehirns ist bei hypotrophen Kindern besonders kritisch, da diese bei der Geburt über sehr geringe Kohlenhydratreserven verfügen.

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Summary During the first two days after birth glycerol, free fatty acids and glucose were determined in plasma respectively blood in 10 hypotrophic newborns (birthweight under 2,500 g and with a normal length of pregnancy).Immediately after birth glycerol and free fatty acids are increasing, the level of glycerol being higher than in premature newborns with a comparable birthweight. The increase of free fatty acids is not significant. It was found that at a lower body temperature the level of fatty acids is lower in the first hours after birth, whereas at a normal body temperature the fatty acid levels are increased.There were no significant changes in the blood glucose levels. Already the first measured dates are low in hypotrophic newborns.The elimination of intravenously applied glycerol was determined. In comparison with premature newborns and those with normal weight the glycerol elimination is accelerated. This can be taken as an increased utilisation. It is discussed how much endogenously produced glycerol (hydrolysis of triglycerides) in the metabolism of hypotrophic newborns is used directly as a source of energy. Especially the supply of the brain with energy is very jeopardized in hypotrophic newborns, since they have only very little sources of energy at birth available.

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Teilweise mit Unterstützung durch die Deutsche Forschungsgemeinschaft, Wo 69/7.

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Für Sachbeihilfen danken wir außerdem der Fa. Humana-Milchwerke, Herford i. Westf.

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Stipendiat der Alexander von Humboldt-Stiftung, 1966; ständige Anschrift: Institut für Mutter und Kind, Prag-Podoli.     

Time course of anoxia-induced K+ concentration changes in the cochlea measured with K+ specific microelectrodes

Summary The endocochlear potential (EP), potassium concentration in the endolymph (K _e ⁺ ) and in the perilymph (K _p ⁺ ) were measured in guinea-pigs during anoxia of different duration. Specific K⁺ doublebarrel microelectrodes with liquid ion exchanger were used. The resting K⁺ concentration in the endolymph was 146.8±9.2 mM and in the perilymph 3.2 ±0.5mM.The following time course of events was observed in the cochlea during anoxia: 40–50 s after the arrest of ventilation the K⁺ concentration decreased by 0.1–0.2 mM in the scala vestibuli, which was time related to a rapid fall of EP to negative values. Perilymphatic K⁺ started to increase in both scalae with a latency of 2–2.5 min, reaching a concentration of about 14 mM 60 min after the arrest of ventilation. The endolymphatic K⁺ began to decrease after a latency of 2.5–3 min, and 60 min after the arrest of ventilation an 80% concentration (average 112 mM K⁺) was reached as compared to the initial value.From the comparison of K⁺ concentration changes with the experimental values of the negative EP, it may be assumed that the negative EP is mainly generated by the K⁺ gradient between the perilymph and endolymph.     

Venlafaxine occupation at the noradrenaline reuptake site: in-vivo determination in healthy volunteers

Venlafaxine, a serotonin and noradrenaline reuptake inhibitor, is an effective antidepressant at doses of 75 mg p.o. daily and above. Preclinical and healthy volunteer studies have demonstrated that venlafaxine is more potent at the serotonin than at the noradrenaline reuptake site, with noradrenergic blocking effects being observed at doses >75 mg p.o. in man. We used the Multiple Organs Coincidences Counter and [11C] meta hydroxy ephedrine (MHED) to test whether significant occupation of cardiac sympathetic neurones was achieved in man in vivo after the acute administration of venlafaxine 75 mg p.o. in nine healthy volunteers. MHED is a tracer which binds at the noradrenaline reuptake site. This study demonstrates that the [11C]MHED signal is significantly reduced after the administration of venlafaxine 75 mg p.o. thus showing that noradrenaline reuptake blockade is observable at this dose. This effect is predominantly seen in volunteers who received > 1 mg/kg venlafaxine.     

The phenotype of ascitic fluid lymphocytes in patients with ovarian carcinoma and other primaries.

BACKGROUND: Ascitic tumor-infiltrating lymphocytes (TIL) are a potential source of effectors for adoptive immunotherapy. PATIENTS AND METHODS: The TIL phenotype was examined by two-color flow cytometry in malignancy-related ascites of 49 patients with different primaries. Interleukin-10 (IL-10) and neopterin were determined in ascitic fluid by enzyme-linked immunoassay. RESULTS: Malignant melanoma patients had significantly higher CD3(+), CD3(+)CD8(+) and CD3(+)CD95(+), and lower CD3(+)CD4(+) lymphocyte numbers than patients with other primaries. Ovarian cancer patients had higher CD3(+)CD45RO(+), CD8(+)CD28(+), CD19(+)CD86(+), CD19(+) and CD19(+)CD86(+) lymphocyte numbers, and lower NK cell numbers than patients with gastrointestinal and pancreatic primaries. Pretreated patients had significantly lower concentrations of IL-10, lower CD8(+)CD28(+), CD3(+)CD45RA(+), and higher CD3(+)CD80(+) numbers than chemotherapy-na?ve patients. Patients with hepatic metastases had lower CD3(+), CD3(+)CD4(+) and CD3(+)CD45RO(+), and higher CD3(+)CD25(+) and NK cell numbers than patients without liver metastases. A substantial number of cells exhibited dendritic cell phenotype. Significant correlations were observed between neopterin and IL-10 concentrations, and numbers of CD8(+)CD28(+) and CD3(+)CD80(+) lymphocytes. CONCLUSIONS: Some parameters of TIL phenotype differ depending on primary, previous treatment, or the presence of liver metastases. A negative correlation was observed between IL-10 and neopterin, and an opposing effect of local concentrations of IL-10 and neopterin on the numbers of CD8(+)CD28(+) and CD3(+)CD80(+) was noted.     

Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines

ObjectivesThe aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.Materials and methodsA national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed.ResultsPrognostic factors significantly associated with poor overall survival in a multivariable Cox model included the time from diagnosis to the start of treatment with TKIs<1 year, increased neutrophil counts, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. The parameters showing statistically significant association with progression-free survival included time from diagnosis to the beginning of treatment with TKI<1 year, increased lactate dehydrogenase, and Eastern Oncology Cooperative Group performance status 2 or higher. We have also validated the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model in our cohort of patients.ConclusionWe demonstrate that the International Database Consortium prognostic model performs well for European patients treated with TKIs, including sunitinib or sorafenib, after progression on cytokines and suggest that a reduction from original 6 down to 4 parameters is possible.