Isolated hypoxic hepatic perfusion with tumor necrosis factor-alpha, melphalan, and mitomycin C using balloon catheter techniques: a pharmacokinetic study in pigs

OBJECTIVE: To validate the methodology of isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques and to gain insight into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and mitomycin C (MMC) through the regional and systemic blood compartments when applying these techniques. SUMMARY BACKGROUND DATA: There is no standard treatment for unresectable liver tumors. Clinical results of isolated limb perfusion with high-dose TNF and melphalan for the treatment of melanoma and sarcoma have been promising, and attempts have been made to extrapolate this success to the isolated liver perfusion setting. The magnitude and toxicity of the surgical procedure, however, have limited clinical applicability. METHODS: Pigs underwent IHHP with TNF, melphalan, and MMC using balloon catheters or served as controls, receiving equivalent dosages of these agents intravenously. After a 20-minute perfusion, a washout procedure was performed for 10 minutes, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the hepatic and systemic blood compartments and concentrations of perfused agents were determined. RESULTS: During perfusion, locoregional plasma drug concentrations were 20- to 40-fold higher than systemic concentrations. Compared with systemic concentrations after intravenous administration, regional concentrations during IHHP were up to 10-fold higher. Regional MMC and melphalan levels steadily declined during perfusion, indicating rapid uptake by the liver tissue; minimal systemic concentrations indicated virtually no leakage to the systemic blood compartment. During isolation, concentrations of TNF in the perfusate declined only slightly, indicating limited uptake by the liver tissue; no leakage of TNF to the systemic circulation was observed. After termination of isolation, systemic TNF levels showed only a minor transient elevation, indicating that the washout procedure at the end of the perfusions was fully effective. CONCLUSIONS: Complete isolation of the hepatic vascular bed can be accomplished when performing IHHP using this balloon catheter technique. Thus, as in extremities, an ideal leakage-free perfusion of the liver can now be performed, and repeated, without major surgery. The effective washout allows the addition of TNF in this setting

A probabilistic threshold model: Analyzing semantic categorization data with the Rasch model

According to the Threshold Theory (Hampton, 1995, 2007) semantic categorization decisions come about through the placement of a threshold criterion along a dimension that represents items' similarity to the category representation. The adequacy of this theory is assessed by applying a formalization of the theory, known as the Rasch model (Rasch, 1960; Thissen & Steinberg, 1986), to categorization data for eight natural language categories and subjecting it to a formal test. In validating the model special care is given to its ability to account for inter- and intra-individual differences in categorization and their relationship with item typicality. Extensions of the Rasch model that can be used to uncover the nature of category representations and the sources of categorization differences are discussed

Isolated Hypoxic Hepatic Perfusion with Retrograde Outflow in Patients with Irresectable Liver Metastases; A New Simplified Technique in Isolated Hepatic Perfusion

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic h

Search for neutral B meson decays to two charged leptons

The decays $\mathrm{B_d^0,\,B_s^0 \rightarrow e^+e^-,\,\mu^+\mu^-,\, e^\pm\mu^\mp}$ are searched for in 3.5 million hadronic ${\mathrm{Z}}$ events, which constitute the full LEP I data sample collected by the L3 detector. No signals are observed, therefore upper limits at the 90\%(95\%) confidence levels are set on the following branching fractions: % \begin{center}% {\setlength{\tabcolsep}{2pt} \begin{tabular}{lccccclcccc}% % Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $1.4(1.8)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^+e^-}}}})$ & $<$ & $5.4(7.0)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $1.0(1.4)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow \mu^+\mu^-}})$ & $<$ & $3.8(5.1)$ & $\times$ & $10^{-5}$; \\% Br$({\mathrm{B_d^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $1.6(2.0)$ & $\times$ & $10^{-5}$; & \hspace*{5mm} & Br$({\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}})$ & $<$ & $4.1(5.3)$ & $\times$ & $10^{-5}$. \\% % \end{tabular}% } \end{center}% % The results for ${\mathrm{B_s^0\rightarrow{\mathrm{e^+e^-}}}}$ and ${\mathrm{B_s^0 \rightarrow {\mathrm{e^\pm\mu^\mp}}}}$ are the first limits set on these decay modes

Study of the Weak Charged Hadronic Current in b Decays

Charged and neutral particle multiplicities of jets associated with identified semileptonic and hadronic b decays are studied. The observed differences between these jets are used to determine the inclusive properties of the weak charged hadronic current. The average charged particle multiplicity of the weak charged hadronic current in b decays is measured for the first time to be 2.69$\pm$0.07(stat.)$\pm$0.14(syst.). This result is in good agreement with the JETSET hadronization model of the weak charged hadronic current if 40$\pm$17\% of the produced mesons are light--flavored tensor (L=1) mesons. This level of tensor meson production is consistent with the measurement of the $\pi^0$ multiplicity in the weak charged hadronic current in b decays. \end{abstract

Analyzing experimental data using the Rasch model

We present a method for studying experimental data based on a psychometric model, the "Rasch model" (Rasch, 1966; Thissen & Steinberg, 1986). We illustrate the method with the use of a data set in the field of concept research. More specifically, we investigate whether a conjunctive concept can be seen as an additive combination of its constituents. High correlations between model and data are obtained, but a formal goodness-of-fit test indicates that the model does not completely account for the data. We then alter the Rasch model in such a way as to capture our idea of why the model deviates from the data. This results in higher correlations and a strong increase in goodness-of-fit. It is concluded that our ideas, as incorporated in the model, adequately summarize the data. More generally, this research illustrates that applying the Rasch model and altering it according to one's hypotheses is an excellent way to analyze experimental data

The instantiation principle re-evaluated

Three experiments are presented in which different aspects concerning Heit and Barsalou's (1996) instantiation principle were investigated. Mean typicalities of subordinate categories within superordinates were predicted very accurately for all investigated concepts. Multiple instantiations were shown to yield somewhat better predictions than single instantiation. The instantiation principle also successfully predicted mean typicalities on a different level (i.e., in lower-level concepts). An alternative account of Heit and Barsalou's findings was also proven wrong. Finally, correspondence between empirically obtained and predicted standard deviations is argued to be dubious, because of several possible sources of bias in the observed and predicted values.Afdeling Psychodiagnostiek en psychologische begeleiding. Onderzoeksgroep Hogere cognitie en individuele verschillen. Onderzoeksgroep Kwantitatieve- en persoonlijkheidspsychologie.status: publishe