The liver has a large capacity for regeneration after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSCs) to participate in liver regeneration. Here we report on three patients subjected to intraportal administration of autologous CD133 + BMSCs subsequent to portal venous embolization of right liver segments, used to expand left lateral hepatic segments as FLRV. Computerized tomography scan volumetry revealed 2.5-fold increased mean proliferation rates of left lateral segments compared with a group of three consecutive patients treated without application of BMSCs. This early experience with portovenous application of CD133 + BMSCs could suggest that this novel therapeutic approach bears the potential of enhancing and accelerating hepatic regeneration in a clinical setting. Stem Cells 2005;23:463-470

In patients with malignant liver lesions, the combination of PVE with CD133(+) BMSC administration substantially increased hepatic regeneration compared with PVE alone.

An expression vector was designed to test the structural requirements of the gp41 N terminus for human immunodeficiency virus type 1-induced membrane fusion. Mutations in the region coding for the N terminus of gp41 were found to disrupt glycoprotein expression because of deleterious effects on the Rev-responsive element (RRE). Insertion of an additional RRE in the 3-noncoding sequence of env made possible efficient glycoprotein expression, irrespective of the mutations introduced into the RRE in the natural location. This permitted the insertion of the unique restriction site SpeI within the N-terminal sequences of gp41, allowing convenient and efficient mutation of the gp41 N terminus by using double-stranded synthetic oligonucleotides. Mutants with deletions of 1 to 7 amino acids of the N terminus were constructed. Expression and cleavage of all mutants were confirmed by Western immunoblot analysis with anti-gp41 antibodies. The capability of mutants to induce membrane fusion was monitored following transfection of HeLa-T4 ؉ cell lines with wild-type and mutant expression vectors by electroporation and microinjection. The efficiency of cell-fusing activity decreased drastically with deletion of 3 and 4 amino acids and was completely lost with deletion of 5 amino acids. Cotransfection of the parent and mutant expression vectors resulted in reduced cell-fusing activity. The extent of this dominant interference by mutant glycoprotein paralleled the decrease in cell-fusing activity of the mutants alone. This suggests the existence of a specific N-terminal structure required for fusing activity. However, there does not appear to be a stringent requirement for the precise length of the N terminus. This finding is supported by the length variation of this region among natural human immunodeficiency virus type 1 isolates and is in contrast to the apparent stringency in the length of analogous N-terminal structures of influenza A virus and paramyxovirus fusion glycoproteins.

Carrying out a 1,000 patient prospective, randomized study comparing a roller pump and the BioMedicus centrifugal pump (CP), hematological parameters, blood loss, renal function, postoperative complications, and lethality data were evaluated. Using a validated preoperative risk stratification method (Cardiac RiskMaster), patients were divided into different risk categories for statistical analysis. This study verified an improved outcome with the use of a CP in routine cardiac surgery, demonstrated by blood handling, blood loss, renal function, and nephrological complication data. There was also a significant reduction in neurological complications. There was no significant difference in postoperative lethality, but high risk patients demonstrated outcomes comparable to those being defined for medium risk patients. Routine cardiac surgical patients as well as multimorbid patients benefit from the use of a CP. Preoperative risk stratification is a valid tool to demonstrate how the employment of new technologies can provide for an improved outcome without increasing overall costs at the same time.

We determined the factors leading to emergency department (ED) delays in patients with acute stroke. Data were collected prospectively in four Berlin inner-city hospitals by ED documentation, medical records, imaging files and patient interviews. An extended Cox proportional hazards model was fitted to the data. Analyses were performed in 558 patients with confirmed diagnosis of stroke. Median time from admission at ED to beginning of computed tomography/magnetic resonance imaging (CT/MRI) was 108 min. In a subgroup of patients potentially eligible for thrombolysis with a pre-hospital delay <120 min and a National Institutes of Health Stroke Scale (NIHSS) >4 (n = 74), the median interval to imaging was 68 min. Multivariable analysis revealed that a more severe initial NIHSS, a pre-hospital delay <3 h, admission at two specific hospitals, admission at weekends, and private health insurance were significantly associated with reduced delays. In stroke patients, the time interval between ED admission and imaging depends both on factors that emerge from clinical needs and on factors independent of clinical necessities. Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for both improvement of in-hospital management and of medical and non-medical factors influencing pre-hospital delays.