Stephen Girard (1750–1831): a one-eyed American patriot

Stephen Girard trader, banker, millionaire, and patriot lived 81 full and exciting years. Apparently born with a blind or amblyopic right eye, he emigrated from Bordeaux. France, via Santa Domingo to the United States, and finally settled in Philadelphia, where he developed a successful maritime trade. Ultimately, Girard became the first multimillionaire in the United States. Extremely generous, he often walked from his home in the center of Philadelphia to his farm in what is now South Philadelphia distributing shoes to needy children. Probably Girard’s most heroic gestures were his gallant fight against the yellow fever epidemic in 1793 and his loan to the U.S. government during the War of 1812, which allowed the bankrupt country to continue the conflict and ultimately to win the war. Presented, in part, at the tenth annual meeting of the David G. Cogan Ophthalmic History Society, the College of Physicians of Philadelphia, March 8 and 9, 1997.     

Origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and the pulvinar in the rabbit

The origins of the projections of the superior colliculus to the dorsal lateral geniculate nucleus and to the pulvinar in Dutch-belted rabbits were investigated using horseradish peroxidase (HRP) methods. Following injections of HRP in the dorsal lateral geniculate nucleus, retrogradely labeled neurons were found in the upper two-thirds of the stratum griseum superficiale of the ipsilateral superior colliculus. Most of the labeled somata were spindle-shaped, and their major axes tended to be perpendicular to the surface of the superior colliculus. In contrast, following injections of the pulvinar, labeled neurons were found in the lower third of the ipsilateral stratum griseum superficiale. In these cases, the labeled somata were larger than those labeled following dorsal lateral geniculate injections and were multipolar in shape.     

Increased antigen-induced local and systemic mediator release in rhinitis subjects with pulmonary symptoms in the pollen season

In order to delineate parameters that might discriminate between allergic subjects who develop R or R-P symptoms during natural antigen exposure, 26 subjects allergic to grass or ragweed pollen were classified into R or R-P groups, and then the antigen sensitivity and degree of in vivo mediator release were compared. Antigen-skin sensitivity was quantitated by dilutional skin-test titration, and bronchial sensitivity was quantitated by the amount of inhaled antigen required to receive the FEV1 by 20%. Mediator release was determined by measuring the amount of histamine that was released into skin chambers during antigen incubation and the rise in plasma histamine and serum NCA during antigen-induced bronchospasm. Compared to the 13 R subjects, the 13 R-P subjects were: (1) more sensitive to antigen by both skin-test and inhalation challenge, (2) responded to inhalation of antigen with a greater fall in FEV1 and a greater rise in serum NCA and plasma histamine, and (3) released more histamine into skin chambers after antigen incubation. Even when R and R-P subjects were matched by comparing only subjects with equal skin sensitivity to antigen, greater increases in serum NCA and plasma histamine occurred after inhalation of antigen in the R-P subjects. These data are consistent with the hypothesis that allergic rhinitis subjects who develop pulmonary symptoms during natural pollen exposure are more sensitive to antigen and release more mediators in response to antigen administration. It is therefore possible that the degree of mediator release may be an important factor in determining the pattern of clinical responses to antigen exposure.     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.     

Early splenectomy and polychemotherapy versus polychemotherapy alone in chronic myeloid leukemia

The effect of early splenectomy and of polychemotherapy with hydroxyurea, busulfan, and alternate bimonthly courses of arabinosyl cytosine and vincristine plus prednisone, was evaluated in 139 previously untreated patients with chronic myeloid leukemia (CML), consecutively admitted to 18 hospitals from March 1973 to October 1974. Fifty-six patients were splenectomized and 83 patients were not splenectomized. Splenectomy did not influence the duration of chronic and blastic phase, and did not prolong survival. The prognosis of high risk patients was not improved. During the chronic phase, high platelet counts were more frequent in splenectomy group, and five patients developed thrombotic or thromboembolic complications, 5 to 19 months after the operation. The median survival of the whole group was 50 months, with 32 of 139 patients (actuarial proportion 30%) remaining alive 72 months after diagnosis, but the slope of the survival curve was similar to that of historical controls. The results of this trial suggests that new strategies should be developed for the therapy of CML.     

Bcr/abl融合基因及Ph染色体检测在慢性髓系白血病中的临床意义

目的探讨慢性髓系白血病(CML)细胞中Ph染色体阳性细胞与bcr/abl融合基因表达之间的关系及临床意义.方法用热变性姬姆萨R显带(RHG)技术和逆转录筑巢式聚合酶链反应(RT-nest-PCR)对171例CML患者的骨髓或外周血单个核细胞进行了分析,并对其中17例行异基因骨髓移植(Allo-BMT)患者进行短期随访.结果154例未经异基因造血干细胞移植(allo-PBSCT)的CML患者中142例(92.2%)为Ph染色体阳性,146例(94.8%)表达bcr/abl mRNA,2种方法结果一致者142份(92 2%).17例患者allo-BMT后1～24个月,仅1例出现Ph阳性,12月后RT-PCR分析结果10例阴性,7例阳性.结论2种方法各有其优缺点,在CML患者的诊断和治疗监测中,宜将细胞遗传学分析与PCR方法相结合.allo-BMT是目前治疗CML的最佳方法之一.     

费城染色体阳性成年急性淋巴细胞白血病患者治疗效果及预后因素分析

目的 分析费城染色体阳性(Ph+)的成年急性淋巴细胞白血病(ALL)患者治疗效果及预后影响因素.方法 回顾性分析49例Ph+ALL患者的临床资料,探讨治疗效果及不同因素对预后的影响.结果49例患者中,男性24例,女性25例;中位年龄38岁(15~77岁),酪氨酸激酶抑制剂(TKI)治疗组血液学完全缓解(CR)率、主要分子生物学反应(MMR)率及完全分子生物学缓解(CMR)率均高于单纯化疗组(96.8 %比72.2 %,64.5 %比16.7 %,25.8 %比11.1 %),差异均有统计学意义(χ2=4.308,P=0.038;χ2=10.468,P=0.001;χ2=4.250,P=0.039).生存分析提示中位总生存(OS)时间为24个月(3~70个月),3年OS率及无复发生存(RFS)率分别为32.7 %、21.4 %;TKI治疗组3年OS率及1年RFS率高于单纯化疗组(40.3 %比11.1 %,67.8 %比11.1 %),差异有统计学意义(χ2=12.725, P<0.001;χ2=17.401,P<0.001);异基因造血干细胞移植(allo-HSCT)组3年OS率及RFS率高于非移植组(62.5 %比25.7 %、41.7 %比15.0 %),差异有统计学意义(χ2=6.196,P=0.013;χ2=8.032,P=0.005);经2个疗程治疗后达MMR组3年OS率及RFS率分别为45.1 %和28.9 %,高于未达MMR组(17.6 %和11.7 %),差异有统计学意义(χ2=5.446,P=0.020;χ2=6.484,P=0.011);Cox多因素分析结果显示,联合TKI治疗(HR=0.227,95 % CI 0.094~0.550,P=0.001)是OS的独立预后因素;联合TKI治疗(HR=0.225,95 % CI 0.082~0.618,P=0.004)及移植(HR=0.275,95 % CI 0.077~0.983,P=0.047)是RFS的独立预后因素.结论 联合TKI治疗能提高患者CR、MMR及CMR率,提高长期生存,为患者接受移植提供更多机会;在TKI时代,移植仍是治疗Ph+ALL的重要方法,尤其那些经化疗联合TKI治疗但早期未达MMR者预后差,应尽早行造血干细胞移植.     

达沙替尼联合甲氨蝶呤和左旋门冬酰胺酶挽救性治疗费城染色体阳性急性淋巴细胞白血病致重度药物性肝损伤一例并文献复习

目的提高对达沙替尼联合大剂量甲氨蝶呤（HD-MIX）和左旋门冬酰胺酶（L-Asp）方案挽救性治疗费城染色体阳性急性淋巴细胞白血病（Ph^＋ALL）致重度药物性肝损伤的认识。方法报道达沙替尼联合HD-MTX及L-Asp方案挽救性治疗Ph^＋ALL致重度药物性肝损伤1例并文献复习。结果此例Ph^＋ALL患者在该方案化疗后第7天暴发重度药物性肝损伤,肝功能：总胆红素（TBIL）221．7μmol／L,直接胆红素（DBIL）156．1μmol／L,间接胆红素（IBIL）65．6μ mol／L,丙氨酸氨基转移酶（ALT）111U／L,天冬氨酸氨基转移酶（AST）131U／L,碱性磷酸酶（ALP）354U／L,谷氨酰转肽酶（GGT）256U／L,总胆汁酸（TBA）199．2μmol／L。经积极保肝治疗2周后,胆红素及氨基转移酶降至正常,且疾病达完全缓解。结论达沙替尼联合HD-MTX及L-Asp方案挽救性治疗Ph^＋ALL疗效显著,但三药均有明显肝脏毒性,联合使用时应注意暴发性药物性肝损伤的发生。     

T‐cell‐rich HLA‐haploidentical hematopoietic stem cell transplantation for relapsed/refractory pediatric Philadelphia chromosome‐positive acute lymphoblastic leukemia without posttransplant tyrosine kinase inhibitor therapy

Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph‐ALL). However, the prognosis of cases of relapsed or refractory Ph‐ALL remains poor. Here, we aimed to assess the efficacy of T‐cell‐rich HLA‐haploidentical hematopoietic stem cell transplantation (TCR‐haplo‐HSCT) in eight patients with relapsed or refractory pediatric Ph‐ALL. Transplant‐related mortality was observed in two patients. All patients discontinued TKI after receiving TCR‐haplo‐HSCT. The 3‐year probability of overall survival and event‐free survival was 75.0 and 62.5%, respectively. These results indicate the efficacy of TCR‐haplo‐HSCT for relapsed/refractory pediatric Ph‐ALL.     

Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome‐positive acute myeloid leukemia: A case report

Philadelphia chromosome‐positive acute myeloid leukemia (Ph + AML) is a rare type of AML with a low survival rate and poor prognosis. We first report a Ph + AML patient who remained in long‐term remission after the combination of flumatinib and venetoclax, which could provide corresponding treatment ideas for clinical practice.