Total Aortic Arch Replacement: Superior Ventriculo-Arterial Coupling with Decellularized Allografts Compared with Conventional Prostheses.

BACKGROUND: To date, no experimental or clinical study provides detailed analysis of vascular impedance changes after total aortic arch replacement. This study investigated ventriculoarterial coupling and vascular impedance after replacement of the aortic arch with conventional prostheses vs. decellularized allografts. METHODS: After preparing decellularized aortic arch allografts, their mechanical, histological and biochemical properties were evaluated and compared to native aortic arches and conventional prostheses in vitro. In open-chest dogs, total aortic arch replacement was performed with conventional prostheses and compared to decellularized allografts (n = 5/group). Aortic flow and pressure were recorded continuously, left ventricular pressure-volume relations were measured by using a pressure-conductance catheter. From the hemodynamic variables end-systolic elastance (Ees), arterial elastance (Ea) and ventriculoarterial coupling were calculated. Characteristic impedance (Z) was assessed by Fourier analysis. RESULTS: While Ees did not differ between the groups and over time (4.1+/-1.19 vs. 4.58+/-1.39 mmHg/mL and 3.21+/-0.97 vs. 3.96+/-1.16 mmHg/mL), Ea showed a higher increase in the prosthesis group (4.01+/-0.67 vs. 6.18+/-0.20 mmHg/mL, P<0.05) in comparison to decellularized allografts (5.03+/-0.35 vs. 5.99+/-1.09 mmHg/mL). This led to impaired ventriculoarterial coupling in the prosthesis group, while it remained unchanged in the allograft group (62.5+/-50.9 vs. 3.9+/-23.4%). Z showed a strong increasing tendency in the prosthesis group and it was markedly higher after replacement when compared to decellularized allografts (44.6+/-8.3dyn.sec.cm-5 vs. 32.4+/-2.0dyn.sec.cm-5, P<0.05). CONCLUSIONS: Total aortic arch replacement leads to contractility-afterload mismatch by means of increased impedance and invert ventriculoarterial coupling ratio after implantation of conventional prostheses. Implantation of decellularized allografts preserves vascular impedance thereby improving ventriculoarterial mechanoenergetics after aortic arch replacement

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A

Since cyclosporin A (CsA) is an immuno-suppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1 + (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1 + DR + cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1 + DR + ), were also reduced after CsA, epidermal non-Langerhans CD1 - DR + cells (macrophages, activated T cells, DR - keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1 + DR + Langerhans cells/non-Langerhans CD1 - DR + epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1 - DR + cells while leaving LC relatively intact in the epidermis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47242/1/403_2004_Article_BF00431054.pd

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events

Sclerotherapy in extrahepatic portal venous obstruction.

One hundred and twenty two patients who presented with variceal bleeding as a result of extrahepatic portal vein obstruction (EHPO) were entered into the sclerotherapy programme with a mean follow up of 23.69 months (range four to 60 months). Eighteen (14.7%) patients were lost to follow up, three (2.4%) patients underwent surgery, and six (4.9%) patients died. Variceal obliteration was achieved in the remaining 95 patients requiring 5.4 (2.4) sessions of sclerotherapy (range 2-18). Seventeen episodes of upper gastrointestinal bleed occurred in 15 patients during sclerotherapy. Recurrence of oesophageal varices was seen in 15 patients. Ten patients developed bulbous gastric varices after obliteration. Major complications including perforation and strictures were seen more commonly in children. Sclerotherapy was associated with a significant reduction in the bleeding rate (bleeds/month/patient) as compared with the presclerotherapy period (p less than 0.001). Endoscopic sclerotherapy is an effective and safe modality in the prevention of variceal bleeds in patients with extrahepatic portal vein obstruction

Psoriatic skin reveals the in vivo presence of an epidermal IL-1 inhibitor

Production of inhibitor(s) of IL-1 activity can be induced in keratinocytes by exposure to UVB. We describe in this study the characterization of an endogenous constitutively expressed IL-1 inhibitor which is present in extracts of human psoriatic epidermal keratome biopsies. Size-fractionated extracts of normal human epidermis did not reveal IL-1 inhibitory factor(s) activity in normal epidermis. Psoriatic epidermal extracts, however, contained virtually no IL-1 bioactivity and inhibited the activity of recombinant human IL-1β. This IL-1 inhibitor has a molecular weight of approximately 30 kDa and a pI of 5.3, as revealed by fast protein liquid chromatography size fractionation and chromatofocusing of psoriatic epidermal extracts. IL-1 inhibitory activity was not blocked by neutralizing anti-TGFβ monoclonal antibody. It did not have any inhibitory effect upon normal cellular proliferation but could block the IL-1 induction of IL-2 production by LBRM.33 cells as late as 4 h after exposure of LBRM.33 cells to IL-1. Thus, in vivo human psoriatic epidermis expresses an IL-1 inhibitor that specifically inhibits IL-1 activity but which appears distinct from previously described UV-induced epidermal IL-1 inhibitory activity or TGFβ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47244/1/403_2004_Article_BF00373372.pd