Location, not staging, of cholangiocarcinoma determines the role for adjuvant chemoradiation therapy

The role of adjuvant chemoradiation therapy (CT/XRT) in the treatment of cholangiocarcinoma is controversial. We undertook this study to determine whether CT/XRT is appropriate after resection of cholangiocarcinomas. One hundred ninety-two patients with cholangiocarcinomas were treated from 1988 to 1999. After resection, patients were assigned a stage (TNM) and were stratified by location of the tumor as intrahepatic, perihilar, and distal tumors. Data are presented as mean +/- standard deviation. Of 192 patients 92 (48%) underwent resections of cholangiocarcinomas. Thirty-four patients had liver resections, 25 had bile duct resections, and 33 underwent pancreaticoduodenectomies. Thirty-four patients had adjuvant CT/XRT, three had adjuvant chemotherapy, four had neoadjuvant CT/XRT, and 50 had no radiation or chemotherapy. Mean survival of resected patients with adjuvant CT/XRT was 42 +/- 37.0 months and without CT/XRT it was 29 24.5 months (P = 0.07). Mean survival of patients with distal tumors receiving or not receiving CT/XRT was 41 +/- 21.8 versus 25 +/- 20.1 months, respectively, (P = 0.04). Adjuvant chemoradiation improves survival after resection for cholangiocarcinoma (P = 0.07) particularly in patients undergoing resection for distal tumors (P = 0.04). Benefits of adjuvant CT/XRT are apparent when stratified by location of cholangiocarcinomas rather than staging.     

Design and fabrication of cast orthopedic implants with freeform surface textures from 3-D printed ceramic shell

Three-dimensional printing is a solid freeform fabrication process, which creates parts directly from a computer model. The parts are built by repetitively spreading a layer of powder and selectively joining the powder in the layer by ink-jet printing of a binder material. 3D printing was applied to the fabrication of sub-millimeter surface textures with overhang and undercut geometries for use in orthopedic prostheses as bony ingrowth structures. 3D printing is used to fabricate ceramic molds of alumina powder and silica binder, and these molds are used to cast the bony ingrowth surfaces of Co-Cr (ASTM F75) alloy. Minimum positive feature sizes of the ceramic mold and, therefore, minimum negative feature sizes of castings were determined to be approximately 200 x 200 x 175 microm and were limited by the strength of ceramic needed to withstand handling. Minimum negative feature sizes in the ceramic mold and, therefore, minimum positive features in the casting were found to be approximately 350 x 350 x 175 microm and were determined by limitations on removal of powder from the ceramic and the pressure required to fill these small features with molten metal during casting. Textures were designed with 5 layers of distinct geometric definition, allowing for the design of overhung geometry with overall porosity ranging from 30-70%. Features as small as 350 x 350 x 200 microm were included in these designs and successfully cast.     

The Role of Regulatory Cells in Miniature Swine Rendered Tolerant to Cardiac Allografts by Donor Kidney Cotransplantation

To determine the mechanism by which cotransplantation of a kidney allograft induces tolerance to a donor heart in miniature swine, we examined the role of CD25⁺ cells in heart/kidney recipients. Tolerance was induced to class‐I MHC mismatched hearts by cotransplanting a donor‐specific kidney with a 12‐day course of cyclosporine. Peripheral blood leukocytes (PBL) were isolated from tolerant heart/kidney recipients and used in cell‐mediated lympholysis (CML) coculture assays as either unmodified PBL, PBL enriched for CD25⁺ cells or PBL depleted of CD25⁺ cells to assess their ability to suppress CML responses of naïve recipient‐matched leukocytes against mismatched target cells. Primed PBL from tolerant heart/kidney recipients completely suppressed lysis by naïve cells. Complete suppression of the response of naïve recipient‐matched leukocytes against donor‐matched target cells was lost following the depletion of CD25⁺ cells from tolerant heart/kidney animal PBL, but it was reestablished by incubation of naïve cells with small populations of CD25⁺ cells from tolerant heart/kidney animals. These data suggest that peripheral blood from tolerant heart/kidney recipients contains regulatory cells that, upon priming, can suppress the response of naïve‐matched PBL in coculture CML assays, and that suppression appears to be dependent on cells expressing CD25.     

Characterization of cutaneous antigen presentation in partially inbred miniature swine

Abstract MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (ARC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8-4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function. EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coatcd petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 × 10⁷ TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous immunity in a manner similar to Langerhans cells in murine or human skin.     

Autonomic cardiovascular responses in antecedent poliomyelitis

Autonomically mediated cardiovascular responses were evaluated in 20 subjects with antecedent poliomyelitis and compared to data from an age- and sex-matched control group. The polio subjects had a lower heart rate response to the Valsalva manoeuvre but the same respiratory sinus arrhythmia as the controls. From this it is concluded that the polio subjects had a normal vagal function. The polio subjects had a greater initial heart rate increase but the same blood pressure response to the orthostatic position as the controls. This indicates a normal function of the sympathetic nerves. The greater heart rate increase is most likely caused by a displacement of blood to the legs because of muscle atrophy. The polio subjects had a smaller blood flow increase as an initial response to an isometric handgrip than the controls. This might be attributed to a reduced beta-adrenergic vasodilation, possibly due to a reduced central vasomotor drive. It is concluded that subjects with antecedent poliomyelitis have no significant dysfunction of the peripheral autonomic nerves. Thus, there is no deterioration of the peripheral autonomic nerve function in parallel with the progressive muscle atrophy and paralysis earlier described in post-polio subjects.     

Vergleichende Herzschallschreibung beim Menschen mit Brustwand- und Oesophagusableitungen

Ohne ZusammenfassungMit 9 Abbildungen in 19 Einzeldarstellungen und 1 Tabelle