Liver enzyme levels, viral RNA, and the immune response against both structural and nonstructural hepatitis C virus (HCV) proteins have been studied in experimentally infected chimpanzees in order to ...further understand the natural history of HCV infection. An ELISA for measuring both IgG and IgM responses to core (c22), 33c (NS3), and c100 (NS4) was employed. The IgG response rates were 5/8 for core, and 8/8 for both 33c and c100. Utilizing this antigen combination, at least one antibody response is measureable at, or within 3 weeks of, the major ALT peak. Although no individual antibody response is universally associated with initial detection of seroconversion, the combination of all three recombinant proteins measures seroconversion an average of 54 days earlier than with c100 alone, in 6/8 of the animals. IgM responses were measureable in 5/8 of the chimpanzees, were of shorter duration, and usually arose concomitantly with IgG responses. IgM appears to be a good indicator of primary infection since neither boosting nor recrudescence of disease during the chronic phase of disease elicited a secondary IgM response. Viral RNA can be measured 4-7 days (average = 9 days) postinfection with the period preceding the ALT peak being characterized by several PCR positive segments interrupted by periods in which no viral RNA can be measured. Following the ALT peak, chronically infected animals with recurring ALT elevations are generally PCR positive with intercedent PCR negative periods. Those animals that appear to have biochemically resolved disease generally have PCR negative profiles, although they still may periodically exhibit PCR positive sera. This indicates that with the recent advent of new screening techniques, a more stringent definition of HCV resolution will be required.
This letter presents a circuit to provide binary phase shift keying to ultra-wideband (UWB) impulse transmitters. The circuit is based on a Gilbert-cell multiplier and uses active on-chip balun and ...unbalanced-to-balanced converters for single-ended to single-ended operation. Detailed measurements of the circuit show a gain ripple of ±1 dB at an overall gain of -2 dB, an input reflection below -12 dB, an output reflection below -18 dB, a group delay variation below 6 ps and a -1 dB input compression point of more than 1 dBm in both switching states over the full 3.1-10.6 GHz UWB frequency range. A time domain measurement verifies the switching operation using an FCC-compliant impulse generator. The circuit is fabricated in a 0.8 ¿m Si/SiGe HBT technology, consumes 31.4 mA at a 3.2 V supply and has a size of 510 × 490 ¿m 2 , including pads. It can be used in UWB systems using pulse correlation reception or spectral spreading.
Aerosol particles of different materials (carbon, brass, and steel) produced by laser evaporation at atmospheric pressure were exposed to an electric field. The primary particles were 1 to 10 nm in ...diameter depending on the target material. It is shown that number concentrations of electrically neutral particles confined in the chamber depend on the field strength. Photomicrographs show the formation of bushlike structures from aerosol particles flowing through the chamber on the electrodes, accompanied by wirelike structures spanning the distance between the electrodes, about 0.5 cm. The wirelike structures continued growing both in number and in width by adding subbranches. The overall structure which filled the volume between the electrodes has certain similarities to an aerogel, which is a nanostructured material with a high void fraction, composed of nanometer particles that are rigidly bonded. However, structures formed by the aerosol process are less rigid and show an anisotropic form, and for this reason are calledaerogel-like.
Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such ...as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non—Fe-) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.
Gallium, when bound to transferrin, has been previously shown to cause tumor cell cytotoxicity by preventing cellular uptake of transferrin bound iron in vitro. Patients treated with constant ...infusion gallium nitrate for carcinoma show a rise in serum iron within 6 hr of the start of treatment. Serum iron returns to baseline by 24 hr post-infusion. Atomic analysis of iron and gallium content of Sephadex G-150 fractions of treatment sera indicate that about an equimolar amount of gallium and iron are associated with transferrin. These gallium and iron concentrations result in inhibition of transferrin mediated iron uptake in vitro, and in vivo allow for > 90% saturation of transferrin with metal. All seven patients who completed two courses of gallium therapy exhibited hypochromic microcytic anemia (mean fall in hemoglobin 3.5 grams %). Evidence for red cell iron depletion was confirmed by an increase (mean 3.3-fold) in zinc protoporphyrin levels. Since transferrin receptor increases on gallium treated iron requiring cells in vitro, we assessed cell surface transferrin receptor on peripheral blood lymphocytes by measuring fluorescent transferrin receptor antibody binding. A population of highly transferrin receptor positive cells peaks at 48 hr into the infusion. DNA analysis as well as double staining indicate the majority of transferrin receptor positive cells are unstimulated B lymphocytes. These studies provide the first documentation that constant infusion gallium treatment results in significant interference with iron metabolism and evidence for tissue iron depletion in vivo. These changes may correlate with therapeutic effects of gallium such as tumor response.
The transferrin receptor has been isolated from human placenta using immunochromatography and affinity chromatography. The receptor is a glycoprotein and has a Mr = 90,000 on sodium dodecyl ...sulfate-gel electrophoresis in the presence of 2-mercaptoethanol. The isolated receptor is immunologically related to the transferrin receptor on the reticulocyte cell surface.
Fragestellung:
Die Tumordokumentation ist für Qualitätssicherung onkologischer Behandlungen sowie als Quelle zuverlässiger Information über die sektorübergreifende Versorgung essentiell. Am Beispiel ...der Mammakarzinomerkrankung wird untersucht, welcher Dokumentationsaufwand und damit verbundener Ressourcenverbrauch besteht.
Methodik:
Die Versorgungskette bei Patientinnen mit primärem Mammakarzinom in standardisierter Erkrankungssituation wurde von initialer Diagnostik bis Abschluss der Nachsorge definiert. Nach Pilotphase am Universitäts-Brustzentrum Franken erfolgte eine multizentrische Validierung (n = 8 Zentren) mit Unterstützung des Bundesgesundheitsministeriums. Die Dokumentationszeitpunkte wurden horizontal erhoben und mit Länge und Personalaufwand erfasst.
Ergebnisse:
62% aller Dokumentationszeitpunkte finden im ambulanten Sektor statt, während der Großteil der Dokumentation durch stationäre Einrichtungen erfolgt. Hinter 47% aller Dokumentationszeitpunkte stehen Hauptaspekte der Qualitätssicherung. 21 Fachbereiche und 20 Berufsgruppen sind an der Dokumentation einer Mammakarzinompatientin beteiligt. Das ärztliche Personal hat einen Anteil von 57% der Dokumentationskosten. Innerhalb der Versorgungskette haben insbesondere die Durchführung von Systemtherapien und Strahlentherapien sowie interdisziplinäre Tumorkonferenzen einen relevanten Einfluss auf den Dokumentationsaufwand. In nicht-zertifizierten Zentren zeigt sich ein reduzierter Aufwand und somit geringere Kosten. Je nach Verlauf entstehen Dokumentationskosten zwischen 660 € und 4.135 € pro Patientin von Erstdiagnose bis Abschluss der Nachsorge.
Schlussfolgerungen:
Die Ergebnisse zeigen die Notwendigkeit der Reduktion des Dokumentationsaufwandes – insbesondere für die ärztliche Berufsgruppe. Da von einer Qualitätsverbesserung durch die Zertifizierung mit ihren speziellen Anforderungen auszugehen ist, ergibt sich die Forderung nach einer adäquaten Vergütung für die Dokumentation. Des Weiteren ist es erforderlich eine reduzierte Anzahl an Variablen für die Qualitätssicherung zentral festzulegen und eine flächendeckende berufsübergreifende Dokumentation zu erreichen. Investitionen in einen einheitlichen Datensatz und in Schnittstellenoptimierungen der vorhandenen Dokumentationssysteme sollten erfolgen.
Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with locally advanced breast cancer (LABC). This was a retrospective review of 21 consecutive women who received NACT as ...initial treatment of LABC, followed by surgical excision. The pre- and post-treatment breast specimens and post-treatment axillary lymph nodes with metastases were immunostained to evaluate for proliferative index (PI) (MIB-1 Immunotech) and vascular endothelial growth factor (VEGF) expression (Santa Cruz, CA, clone A-20). Thirteen of the 21 patients (62%) had more than 50% tumor shrinkage following NACT. The breast's mean PI decreased from 47.86% to 23.95% after treatment (P = 0.005). The mean PI in the post-treatment lymph nodes was 24.47%. A nodal post-NACT PI of less than 10% and progesterone receptor-positive tumor status were associated with better survival, as all such patients are alive. A high PI after NACT was associated with recurrence or death. All of the patients who showed an excellent clinical response had either a decrease in the PI or an absence of a high level of VEGF after NACT. Most patients exhibited persistent expression of VEGF after NACT. Pathologic response in the primary tumor did not correlate with the response in the lymph nodes or with overall survival. NACT reduces the size and PI of the primary breast tumor independent of the patient's node status. The PI may be an early means by which to identify tumors most likely to reduce in size with chemotherapy. A low PI after NACT is associated with better survival. There is persistent expression of VEGF in post-NACT residual breast carcinoma. Thus, anti-VEGF drugs after conventional chemotherapy may benefit patients with residual carcinoma.
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