Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study

PurposeOur purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer.Methods and MaterialsWe reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively.ResultsOf 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL.ConclusionsFor patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.     

Standardized molecular typing of Candida albicans strains

Summary. A method is presented for the standardization of Candida albicans DNA fingerprinting, which is based on Southern hybridization of Eco RI-digested chromosomal DNA with the moderately repetitive DNA element CARE-2 and the subsequent rehybridization of the blots with a molecular size marker also included in each DNA sample. This method resulted in extremely precise alignment of all strain-specific CARE-2 hybridization patterns, even when analysed on different gels, and will enhance the accuracy of genetic relationship determinations in epidemiological studies including large numbers of strains.
Zusammenfassung. Zur Standardisierung des DNA-Fingerprinting von Candida albicans wurde eine Methode entwickelt, die auf der Southern Hybridisierung Eco RI-gespaltener chromosomaler DNA mit dem mittelrepetitiven DNA-Element CARE-2 und der darauffolgenden Rehybridisierung der Blots mit einem auch in den Proben enthaltenen molekularen Größenmarker beruht. Dies resultierte in einer äußerst präzisen Größen-bestimmung der hybridisierenden Fragmente, so daß alle stammspezifischen CARE-2-Hybridisierungsmuster exakt verglichen werden konnten, auch wenn die Isolate auf verschiedenen Gelen analysiert wurden. Die Methode erhöht die Genauigkeit der Bestimmung genetischer Verwandtschaftsbeziehungen in epidemiologischen Untersuchungen, in denen eine große Anzahl von Stämmen analysiert wird.     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

Comparison of a neutralization enzyme immunoassay and an enzyme-linked immunosorbent assay for evaluation of immune status of children vaccinated for mumps.

A 50% neutralization enzyme immunoassay (N50-EIA) was compared with an indirect enzyme-linked immunosorbent assay (ELISA) for determining mumps virus antibodies in three consecutive serum samples from 138 children vaccinated with a live mumps vaccine at the age (in years) of 1.5. By the N50-EIA, most (132 of 138) preserum samples did not show neutralizing activity. Eight to 12 weeks after vaccination, 17 of the children were still negative, but only 7 remained so after 2.5 years, resulting in a seroconversion rate of 125 of 132 (95%). Over the same period, the neutralization geometric mean titer rose from 3.6 to 9.9. By an indirect ELISA, 128 of 138 preserum samples were found negative. The early and late postvaccination sera of 8 children were ELISA negative, resulting in a seroconversion rate of 120 of 128 (94%). Only two children remained seronegative by both methods. Seven of the late postvaccination serum samples yielded noncorresponding results, reflecting 95% correlation between both methods. Due to cross-reactivity with parainfluenza viruses, the ELISA proved to be less specific, but on the other hand, it showed a greater sensitivity than the N50-EIA.     

A promising technique for transplantation of bone marrow-derived endothelial progenitor cells into rat heart.

OBJECTIVE: To investigate the feasibility of intracoronary application of endothelial progenitor cells and the subsequent distribution within the heart. METHODS: Endothelial progenitors cells (EPCs) cultured from rat bone marrow were identified by double-positive staining with Dil-Ac-LDL and BS1-lectin. Twenty-four hours before cell transplantation, EPCs were labeled with 5-bromo-2'-deoxyuridine (BrdU). Cells (5 x 10(5) in 250-microl medium) were injected into healthy rats, either as intracoronary application (n=11) or as intramyocardial injection (n = 6). At 15 min or 3 days posttransplantation, hearts as well as other organs (lung, liver, kidney, and spleen) were collected and processed for subsequent BrdU immunohistochemistry. The number of BrdU-positive cells per tissue area was counted. RESULTS: Compared to intramyocardial injection, intracoronary administration resulted in more than twice as much positive cells in the heart (P < .05), with no local differences within the heart. Whereas after 15 min, EPCs were equally distributed in all examined organs (except for the spleen), cells that were still present after 3 days, approximately 10%, were selectively restricted to the heart. CONCLUSIONS: Our data indicate that the intracoronary application provides a promising technique for EPC transplantation in the rat heart.     

Specific T-cell response to a Pneumocystis carinii surface glycoprotein (gp120) after immunization and natural infection.

T cells have been shown to be important in recovery from Pneumocystis carinii pneumonitis, although no specific antigen of P. carinii has been defined as containing T-cell epitopes. P. carinii has an abundant mannosylated surface glycoprotein of approximately 120 kDa (gp120) which induces a prominent host antibody response in experimental animals after exposure to P. carinii in the environment or after recovery from P. carinii pneumonitis. P. carinii gp120 was purified from infected lungs by lectin affinity chromatography. Standard in vitro lymphocyte stimulation assays using purified gp120 and control normal lung preparations were performed on isolated T cells obtained from BALB/c mice after immunization with P. carinii-infected crude lung homogenates or lectin-purified gp120. Lymphocytes from reconstituted severe combined immunodeficient mice which had recovered from naturally acquired P. carinii pneumonitis were also tested. A specific T-cell response was elicited by gp120 after immunization with P. carinii gp120 and after recovery from P. carinii pneumonitis. In addition, the mice developed a strong antibody response to gp120 as ascertained by Western blot (immunoblot). These data suggest that gp120 may be important in the recognition of P. carinii by T cells.     

Requirements for CD4+ cells and gamma interferon in resolution of established Cryptosporidium parvum infection in mice.

The importance of CD4+ cells and gamma interferon (IFN-gamma) in the resolution of established Cryptosporidium parvum infection was investigated with a murine model of cryptosporidiosis in severe combined immunodeficient (SCID) mice. C. parvum-infected SCID mice were reconstituted with spleen cells from immunocompetent donors. The recipients were able to resolve their C. parvum infection by 17 days postreconstitution. Treatment of reconstituted SCID mice with either anti-CD4 monoclonal antibodies to deplete them of CD4+ cells or with anti-IFN-gamma to neutralize IFN-gamma activity reduced or eliminated their ability to resolve C. parvum infection whereas treatment with either anti-CD8 monoclonal antibodies or anti-asialo-GM1 antibodies had no effect. We also found C. parvum-specific antibodies in serum samples from two of four reconstituted SCID mice killed on postreconstitution day 17 but not in unreconstituted SCID mice. Moreover, anti-CD4-treated mice had no detectable specific antibodies to C. parvum, whereas all mice treated with either anti-CD8 or anti-asialo-GM1 had substantial levels of specific antibodies in their serum. Although the role of the specific antibody is not known, these findings clearly indicate that resolution of an established C. parvum infection in immunologically reconstituted SCID mice is dependent on both CD4+ cells and IFN-gamma.     

Comparative evaluation of the VERSANT HCV RNA 3.0, QUANTIPLEX HCV RNA 2.0, and COBAS AMPLICOR HCV MONITOR version 2.0 Assays for quantification of hepatitis C virus RNA in serum

A comparison of quantitative results expressed in hepatitis C virus (HCV) international units per milliliter, obtained from the VERSANT HCV RNA 3.0 (bDNA-3.0) assay, the QUANTIPLEX HCV RNA 2.0 (bDNA-2.0) assay, and the COBAS AMPLICOR HCV MONITOR version 2.0 (HCM-2.0) test was performed. A total of 168 patient specimens submitted to the Mayo Clinic Molecular Microbiology Laboratory for HCV quantification or HCV genotyping were studied. Of the specimens tested, 97, 88, and 79% yielded quantitative results within the dynamic range of the bDNA-3.0, bDNA-2.0, and HCM-2.0 assays, respectively. Overall, there was substantial agreement between the results generated by all three assays. A total of 15 out of 29 (52%) of the specimens determined to contain viral loads of <31,746 IU/ml by the bDNA-3.0 assay were categorized as containing viral loads within the range of 31,746 to 500,000 IU/ml by the bDNA-2.0 assay. Although substantial agreement was noted between the results generated by the bDNA-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-2.0 assay was noted (P = 0.001). Likewise, although substantial agreement was noted between the results generated by the HCM-2.0 and bDNA-3.0 assays, a bias toward higher viral titer by the bDNA-3.0 assay was noted (P < or = 0.001). The discrepancy between the HCM-2.0 and bDNA-3.0 results was more pronounced when viral loads were >500,000 IU/ml and resulted in statistically significant differences (P < or = 0.001) in determining whether viral loads were above or below 800,000 IU/ml of HCV RNA, the proposed threshold value for tailoring the duration of combination therapy. The expression of quantitative values in HCV international units per milliliter was a strength of both the bDNA-3.0 and HCM-2.0 assays.     

IgVH determined genetic restriction of a non-internal image monoclonal anti-idiotypic vaccine against Semliki Forest virus.

Two monoclonal anti-idiotypic antibodies (ab2 mAb), designated 1.13A112 (IgG2a) and 1.13A321 (IgG1) and induced against Semliki Forest virus (SFV)-neutralizing mAb UM 1.13, were investigated with regard to their vaccine potential. 1.13A321 was coupled with glutaraldehyde to keyhole limpet haemocyanin (KLH) and mixed with the adjuvant Quil A. Then when injected subcutaneously into BALB/c mice, it evoked high levels of SFV-neutralizing anti-anti-idiotypic antibodies in serum. In contrast, 1.13A112 had to be indirectly cross-linked to KLH with anti-mouse immunoglobulin to induce a low neutralizing antibody response. Competition binding assay revealed that 1.13A112 and 1.13A321 were completely competitive. Furthermore, SFV neutralization by UM 1.13 and anti-anti-idiotypic (ab3) serum was blocked equally well by either ab2 mAb. These results indicate that ab1 (UM 1.13) and ab3 share at least one antigen-combining site-related idiotope. Induction of SFV-neutralizing antibodies is genetically restricted. Rabbit anti-anti-idiotypic sera against 1.13A321 and 1.13A112 contained no SFV-neutralizing activity. Moreover, in DBA/2, C57BL/6J, CAL-20, and CB-20 mice 1.13A321 did not develop SFV-neutralizing ab3 antibodies in contrast to BALB.K, 129, SWISS, and BAB-14 mice. CAL-20, CB-20, and BAB-14 mice are congenic strains with an inbred background of BALB/c. CB-20 mice derived both IgCH and IgVH from donor strain C57BL/Ka, while BAB-14 mice derived IgCH from C57BL/Ka mice but retained IgVH from BALB/c mice. Clearly, induction of SFV-neutralizing antibodies by 1.13A321 in BAB-14 mice is dependent on IgVH of BALB/c origin. The results suggest that 1.13A321 binds to a paratope-associated recurring idiotope and almost certainly does not bear the internal image of the discontinuous neutralization epitope recognized by mAb UM 1.13. The latter suggestion is sustained by the observation that 1.13A112 and 1.13A321 do not bind to cell receptors.