The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64.

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.     

Importance of speech production for phonological awareness and word decoding: The case of children with cerebral palsy

The goal of this longitudinal study was to investigate the precursors of early reading development in 52 children with cerebral palsy at kindergarten level in comparison to 65 children without disabilities. Word Decoding was measured to investigate early reading skills, while Phonological Awareness, Phonological Short-term Memory (STM), Speech Perception, Speech Production and Nonverbal Reasoning were considered reading precursors. Children with cerebral palsy lag behind on all reading precursors at the beginning of the second year of kindergarten. For the children without disabilities, early reading skills in Grade 1 were best predicted by Phonological Awareness and Phonological STM while Speech Production was the most important predictor of early reading success for the children with cerebral palsy, followed by Phonological Awareness and Speech Perception. Furthermore, for children with cerebral palsy, Speech Production appears to dominate reading development, as Speech Production measured at the beginning of the second year of kindergarten was strongly predictive of all other reading precursors measured at the end of the second year of kindergarten. The results of this study reveal that children with cerebral palsy with additional speech impairments are at risk for limited literacy development. Clinical implications are discussed.     

Wasserstoffzahl und Säuregehalt des Schweißes bei chirurgischen Kranken

Zusammenfassung Die Wasserstoffzahl des Schweißes, der Gehalt an freien Wasserstoffionen, sagt nichts aus über die vorhandenen Säuren und Basen. Die Titrationsacidität, der gehalt des Schweißes an sauren und alkalischen Molekülen, wird durch Titration festgestellt. Wasserstoffzahl und Titrationsacidität im Spontanschweiß von Kranken unterscheiden sich wesentlich von P_H und Titrationsacidität im Wärmeschweiß von Gesunden. Der Spontanschweiß enthält bedeutend mehr Säure und alkalische Substanz; sein P_H bewegt sich in stätker sauren Bereichen und liegt oft tiefer als im Harn. Die Schweißfunktion ist eine Stoffwechselfunktion. Ursache der Schweißsekretion ist eine Stoffwechselstörung. Durch Schwitzen wird bei Bedarf das Stoffwechselgleichgewicht wiederhergestellt. Maßgebend für den Verlauf der Schweiß-P_H-Kurve ist die Intensität des schweißtreibenden Reizes und die Wirksamkeit des inneren Schwitzeffektes. Maßgebend für die Titrationsacidität ist der Allgemeinzustand, insbesondere die Leistungsfähigkeit der übrigen Stoffwechselorgane. Aus Qualität und Quantität des Schweißes können zuverlässige Schlüsse auf die vegetative Gesamtlage gezogen werden. Plötzlicher Absturz und ungewöhnlich hoher Anstieg der P_H-Kurve zeigen kritische Wendepunkte im Krankheitsverlaufe an. Kritische Schweiße und Nachtschweiße enthalten als titrierbare Substanz vorwiegend Säure, Todesschweiße und andere Erstickungsschweiße vorwiegend alkalische Stoffe in hoher Konzentration. Im einstündigen kritischen Schweiß können von Kranken mehr Säuren ausgeschwitzt werden, als im 24 Stundenharn durch die Nieren abgegeben werden. An der Heilwirkung der Schweißfunktion bei Krankheiten hat neben dem inneren Schwitzeffekt, der Vernichtung von Stoffwechselprodukten und Giften im Körper, der äußere Schwitzeffekt, die Ausscheidung von Säure, Toxin, Wasser und Salzen entscheidenden Anteil.Mit 10 Textabbildungen.     

CNQX, a new non-NMDA receptor antagonist, reduces spike wave discharges in the WAG/Rij rat model of absence epilepsy.

The effects on seizures, EEG and behavior of the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), were studied in the WAG/Rij rat with absence epilepsy. Intracerebroventricular injections (10, 50, and 100 nmol/5 microliters CNQX) showed that CNQX decreases the number of spike wave discharges in a dose-dependent way. Coinjection of CNQX (100 nmol/5 microliters) and AMPA (0.1 pmol/5 microliters), kainic acid (0.01 nmol/5 microliters) or NMDA (50 pmol/5 microliters) attenuated the CNQX response, indicating that CNQX acts on both non-NMDA and NMDA receptors. The observed effects appear to be specific manipulations of the epilepsy not mediated by behavioral changes.     

Hemophagocytic syndrome and T-cell lymphoma after kidney transplantation: a case report

Lymphoma in immunocompromised transplant patients is a feared cause of morbidity and mortality. Superimposed on the lymphoma and the transplantation immunosuppression is a rare condition: hemophagocytic syndrome (HS). HS is characterized by fever, hepatosplenomegaly and lymphadenopathy, skin rashes, jaundice, coagulopathy, and phagocytosis of blood elements with pancytopenia. Here we describe a rare but fatal case of a kidney transplant patient who developed T-cell lymphoma and HS, without evidence of EBV replication. A short review of the diagnosis, treatment, and prognosis of HS is given. Received: 4 March 1997 Received after revision: 6 June 1997 Accepted: 30 June 1997     

Asymptomatic autoimmune chronic active hepatitis in a male adolescent

We report a 12-year-old boy presenting with smooth muscle antibody-positive auto-immune chronic active hepatitis. Suspicion of the diagnosis arose after a routine blood test which revealed abnormal liver function tests. In spite of the presence of cirrhosis and patchy necrosis on liver biopsy, our patient never showed any clinical feature of impaired liver function. This observation demonstrates that auto-immune hepatitis may exist for a long time before clinical symptoms appear and probably explains why some cases of auto-immune hepatitis finally present as fulminant liver failure.     

Tumor necrosis factor-alpha in whole blood cultures of preeclamptic patients and healthy pregnant and nonpregnant women.

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is recognized as a likely mediator of the excessive endothelial activation and injury that is a key pathogenetic mechanism of preeclampsia. We used whole blood cell cultures from 12 patients with severe preeclampsia and from 12 healthy pregnant and nonpregnant women to determine the release of TNF-alpha by unstimulated leukocytes as a measure of their state of activation, and their response to stimulation with lipopolysaccharide (LPS) as an indicator of their state of priming. METHODS: Blood was cultivated without and with LPS, and TNF-alpha release was measured after six and 24 hours of cultivation by enzyme-linked immunoassays. Differential leukocyte counts were performed, and TNF-alpha values calculated per 10(5) monocytes. RESULTS: In unstimulated whole blood cultures, TNF-alpha release after six hours of cultivation was similar in all three groups; but after 24 hours, TNF-alpha concentrations in culture supernatants from preeclamptic patients were significantly higher than were values obtained in blood from normotensive pregnant women. In LPS-stimulated blood cultures with a maximum of TNF-alpha release at six hours cultivation time, TNF-alpha concentrations were significantly lower in preeclamptic women than they were in both control groups. We showed in an additional experiment that a strong LPS challenge following preactivation with high doses of LPS resulted in reduced release of TNF-alpha compared with release of TNF-alpha following preactivation with low doses of LPS. CONCLUSIONS: The observed high capacity for spontaneous TNF-alpha release by leukocytes in preeclampsia indicates activation of TNF-alpha producing leukocytes by the disease process. Preactivation and exhaustion of leukocytes by leakage of TNF-alpha could lead to the reduced response to TNF-alpha inducer LPS as observed in blood cultures from preeclamptic patients.