Effect of recombinant granulocyte colony-stimulating factor on neutrophil kinetics in normal young and elderly humans

Recombinant granulocyte colony-stimulating factor (G-CSF) was administered to healthy young (n = 32) and elderly (n = 19) volunteers (0 microgram/d, 30 microgram/d, or 300 microgram/d) to determine its effect on neutrophil production, blood kinetics, and tissue migration. Measurements included blood counts (daily), marrow neutrophil pool sizes and neutrophil tissue migration (baseline and day 5), blood kinetics (day 6), and marrow transit time while on drug (days 6 to 14). G-CSF markedly expanded the marrow neutrophil mitotic pool and shortened the transit time of the postmitotic pool (control, mean = 6.4 days; 300 microgram/d, mean = 2.9 d). G-CSF increased neutrophil production without significantly altering blood neutrophil half-life or margination. Compared to control, neutrophil accumulation in skin chambers decreased by about 50% in the 300 microgram/d group in both young and elderly subjects. G-CSF induced neutrophilia by stimulating proliferation of marrow neutrophil precursors and accelerating neutrophil entry into the blood. Decreased neutrophil inflammatory responses measured with the skin chamber technique may be because of the relative immaturity of the circulating cells or to alterations in neutrophil phenotype induced by G-CSF.     

Immunologic heterogeneity of diffuse large cell lymphoma

The cellular lineage of 57 diffuse large-cell lymphomas (DLCLs) was determined using a panel of monoclonal antibodies directed against lineage-restricted and -associated T, B, and monocyte antigens. The majority (82%) were of B cell lineage as determined by the expression of sig and/or B1, with the remaining 16% being of T cell lineage and 2%, of monocyte-myeloid lineage. By the expression of other B cell- restricted and -associated antigens, two major and two minor subgroups could be identified. These subgroups expressed the following phenotypes: (1) B1+B4+sIG+B2- (51%); (2) B1+B4+sIg+B2+ (29%); (3) B1+B4+sIg-B2+ (10%); and (4) B1+B4-sIg+B2- (10)%. The morphology of transformed lymphocytes, the weak to absent expression of the early B cell antigens B2 and sIgD, and the absence of the late B cell differentiation antigens PCA-1 and PC-1 suggested that these tumors were the neoplastic counterparts of normal B cells at the mid-stages of differentiation. Further support for the notion that B-DLCLs correspond to transformed B lymphocytes was concluded from the observation that B cells could be identified in normal spleen that expressed the cell surface phenotype and morphological appearance of the majority of B- DLCLs.     

Immunohistochemical characterization of a 183 KD myeloid-specific-DNA- binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.     

Biological versus mechanical valves. Analysis of 1,116 valves inserted in 1,012 adult patients with a 4,818 patient-year and a 5,327 valve-year follow-up

All surviving patients between 18 and 88 years of age receiving biological or mechanical prosthetic heart valves at the Yale-New Haven Hospital from January 1974 through January 1985 were analyzed for thromboembolism, anticoagulation-related hemorrhage, endocarditis, perivalvular leak, valve failure, need for reoperation, late cardiac death, and valve-related death. The rates of these events were analyzed in linear and actuarial terms over the 11 year period. A total of 533 patients received 606 biological valves (328 aortic, 252 mitral, 24 tricuspid, and two pulmonary, consisting of 482 Carpentier-Edwards, 108 Hancock, 15 Ionescu-Shiley, and one other), with a mean follow-up of 2,571 patient-years and 2,935 valve-years. They were compared with 479 patients with 510 mechanical valves (330 aortic, 175 mitral, and five tricuspid, consisting of 178 Starr-Edwards, 166 St. Jude Medical, 164 Bj?rk-Shiley, and two others), which were implanted for 2,247 patient-years and 2,392 valve-years. We found a significantly increased incidence of thromboembolism (p less than 0.001) and reoperation for perivalvular leak (p less than 0.05) in the mechanical valves compared with the biological valves, but a significantly increased rate of valve failure (p less than 0.001) in the biological valves compared with the mechanical valves. The overall analysis comparing total morbidity and valve-related mortality significantly (p less than 0.01) favored the biological valves in the first 5 years of the study and the mechanical valves (p less than 0.001) in the second 5 years of the study. However, the net 10 year results showed no significant difference between the two types of valves. In summary, we found little direct evidence to strongly support the generalized use of one type of valve over another.     

Ergotamininduzierte rektovaginale Fistel

Zusammenfassung Grundlagen: Ergotaminpr?parate werden nach wie vor zur Coupierung des akuten Migr?neanfalls eingesetzt. Bei der Anwendung von ergotaminhaltigen Suppositorien k?nnen lokale perianale und rektale Ulzerationen entstehen. Methodik: Wir berichten über eine 39j?hrige Patientin mit einer ergotamininduzierten rektovaginalen Fistel. Ergebnisse: Je nach H?he und Durchmesser der Fistel k?nnen unterschiedliche Verfahren zur chirurgischen Sanierung gew?hlt werden. Bei unserer Patientin haben wir nach Anlage eines Anus praeter transversalis eine transvaginale Exzision mit Schichtverschlu? erfolgreich durchgeführt. Schlu?folgerungen: Der anorektale Ergotismus ist wegen des h?ufig verschweiegenen Abusus und der ungew?hnlichen Manifestation bisher selten diagnostiziert worden.