Coating Membranes for a Sorbent-Based Artificial Liver: Adsorption Characteristics

Techniques are described for the coating of sorbents to be used in an artificial liver support system based on mixed sorbent bed hemoperfusion. Activated charcoal has been coated with cellulose acetate (CA) by solvent evaporation. With Amberlite XAD-4, the Wurster technique was used for coating with CA. XAD-4 has also been coated with a synthetic polyelectrolyte with anticoagulant activity by adsorption and fixation by gamma radiation-induced crosslinking. Activated charcoal, XAD-4, and a cation exchange resin, all in powdered form, were encapsulated in agarose gel beads. Adsorption characteristics onto the sorbents are described. The results are in agreement with a theoretical model presented. In general, adsorption onto XAD-4 is limited by film diffusion. With activated charcoal, pore diffusion limitation is generally observed. Blood compatibility is improved by coatin

Problems in Treating Experimentally Induced Acute Hepatic Failure by Hemoperfusion or Cross Circulation

Acute hepatic failure was induced in rats by galactosamine injection intraperitoneally (1 gm per kg). Twenty-four hours later rats were treated by hemoperfusion (HP) over encapsulated sorbents: cellulose acetate-coated charcoal, polyelectrolyte-coated XAD4, a combination of both, or cross circulation with a healthy donor. Compared with control treatment (prevention of hypoglycemia by glucose infusion), the survival rate was not improved by HP or cross circulation: controls 19% vs. treated animals 0 to 17%. Extension of duration or increased frequency of HP gave the same survival rates. Computer simulation based on zero-order introduction of a possible toxin into a two-compartment model shows that HP up to 5 hr per day is not able to clear the body effectively from the assumed toxin if its partition coefficient exceeds a value of 50

Escape from Surveillance: how leukemic cells subvert the immune system

Ossenkoppele, G.J. [Promotor]Loosdrecht, A.A. van de [Copromotor

Successful treatment of subcutaneously disseminated aspergillosis with caspofungin acetate in an allogeneic peripheral blood stem cell transplantation patient.

We present a patient with acute myeloid leukaemia who developed subcutaneously disseminated aspergillosis after allogeneic peripheral stem cell transplantation (PSCT). Disseminated aspergillosis after stem cell transplantation has a high mortality despite treatment with amphotericin B or one of the azoles. Aspergillosis in our patient was refractory to amphotericin B and itraconazole but was successfully treated with caspofungin acetate

Interobserver variation in CD30 immunohistochemistry interpretation; consequences for patient selection for targeted treatment

AimsCD30 immunohistochemistry (IHC) in malignant lymphoma is used for selection of patients in clinical trials using brentuximab vedotin, an antibody drug-conjugate targeting the CD30 molecule. For reliable implementation in daily practice and meaningful selection of patients for clinical trials, information on technical variation and interobserver reproducibility of CD30 immunohistochemistry (IHC) staining is required. Methods and resultsWe conducted a three-round reproducibility assessment of CD30 scoring for categorised frequency and intensity, including a technical validation, a live polling' pre- and post-instruction scoring round and a web-based round including individual scoring with additional IHC information to mimic daily diagnostic practice. Agreement in all three scoring rounds was poor to fair ( = 0.12-0.35 for CD30-positive tumour cell percentage and = 0.16-0.41 for staining intensity), even when allowing for one category of freedom in percentage of tumour cell positivity ( = 0.30-0.61). The first round with CD30 staining performed in five independent laboratories showed objective differences in staining intensity. In the second round, approximately half the pathologists changed their opinion on CD30 frequency after a discussion on potential pitfalls, highlighting hesitancy in decision-making. Using fictional cut-off points for percentage of tumour cell positivity, agreement was still suboptimal ( = 0.35-0.60). ConclusionsLack of agreement in cases with heterogeneous expression is shown to influence patient eligibility for treatment with brentuximab vedotin, both in clinical practice and within the context of clinical trials, and limits the potential predictive value of the relative frequency of CD30-positive neoplastic cells for clinical response

The pathophysiological basis of pharmacological interventions in CAVD

Calcific aortic valve disease (CAVD) results in aortic valve stenosis and is one of the most common cardiac diseases in both Western and developing countries. The burden of this disease is expected to increase rapidly in the future, but there are still no relevant pharmacological therapies available and aortic valve replacement remains the sole definite therapy. This review presents an overview of the most common causes of CAVD, followed by current debates and trials related to the onset and progression of this disease. Several differences and similarities between the different causes of CAVD are presented. Additionally, stages of CAVD are compared with stages in atherosclerosis. Finally, future directions for research on CAVD will be discussed