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Biomedical subjects

W H Churchill

Publications and source records attributed to W H Churchill.

At least 19 recordsLinked to original sources
PubMed1992

Red cell transfusions in coronary artery bypass surgery (DRGs 106 and 107)

To study red cell transfusion practice in 3216 coronary artery bypass graft (CABG) cases in 11 hospitals in 1988, abstracted patient records were stratified by diagnosis related group (DRG) (that is, DRG 106, coronary artery bypass without catheterization, or DRG 107, coronary artery bypass with catheterization) and International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) surgical procedure code. Means of units per transfused patient, age and length of stay, and in-hospital mortality rates were significantly greater for patients in DRG 106 than DRG 107. Gender was a significant factor for transfusion outcomes; female patients were more likely to undergo transfusion, and, when transfused, they received more units of red cells than male patients. For a given DRG/ICD-9-CM surgical procedure class, significant differences were found between hospitals in the percentage of patients transfused, but not in mean units of red cells per transfused patient. However, within individual hospitals, the proportion of patients transfused and the number of units per transfused patient did not vary significantly across DRG/ICD-9-CM procedure classes. These results suggest that circumstances operating within a hospital, still to be identified, had more influence on transfusion decisions than the nature of the surgical intervention.

Aged↗
PubMed1992

Thawing fresh frozen plasma in a microwave oven. A comparison with thawing in a 37 degrees C waterbath.

We show in this report that fresh frozen plasma (FFP) can be thawed faster using a specifically designed microwave oven (MWO) (WesLabs Plasma Defroster, Westmorland Laboratories, Inc., New Brunswick, Canada) than using 37 degrees C water bath (WB) and that the thawed product was equivalent to FFP thawed by WB. Paired plasma bags (200 mL/bag) from plasma pools were frozen, stored at -35 degrees C, and thawed in parallel, one bag in MWO, the other in WB. Mean thaw time (mean + SD) by MWO was 6.99 + 1.3 minutes; by WB the time was 17.6 + 1.7 minutes (n = 24; P less than 0.005). Rapid calorimetry of thawed plasma showed that MWO-thawed FFP temperature was 20.4 + 2.5 degrees C, whereas WB-thawed FFP was 15.4 + 3.3 degrees C (n = 24; P less than 0.005). Except for thrombin time (MWO = 20.1 seconds; WB = 19.8 seconds; n = 24; P = 0.023), no significant differences were observed in the 23 other coagulation parameters and plasma proteins studied. Faster thawing and freedom from risk of contamination may make MWO the method of choice for emergency thawing of FFP.

Blood Coagulation↗
PubMed1979

The influence of chemotherapy on response of patients with hematologic malignancies to influenza vaccine.

Bivalent influenza vaccine (containing antigens A/Victoria and A/New Jersey) was administered to 52 patients with hematologic malignancies, and pre- and postvaccination antibody titers to both antigens were determined by hemagglutination-inhibition. In comparison to healthy controls, mean antibody titer elevations were lower for both antigens in all disease groups, being significant (p less than 0.05) for A/Victoria in patients with non-Hodgkin's lymphoma, acute leukemia and lymphoproliferative diseases, and for A/New Jersey in patients with Hodgkin's and non-Hodgkin's lymphomas. In comparison to controls, significant depression of antibody response to both antigens was seen in patients on combination chemotherapy (p less than 0.0005), to a lesser extent in patients on daily single alkylating agent chemotherapy (p less than 0.05), while untreated patients did not differ significantly. Lymphopenia and depressed immunoglobulin levels were associated with a higher failure rate in eliciting "protective" greater than or equal to fourfold antibody titer increases. The findings suggest that patients with hematologic malignancies who are receiving chemotherapy at the time of vaccination are unlikely to attain seroconversion to protective antibody levels with influenza vaccine.

Antibodies, Viral↗
PubMed1979

Cytotoxicity of human macrophages for tumor cells. Enhancement by human lymphocyte mediators.

Human macrophages, derived from peripheral blood monocytes, acquire enhanced cytotoxicity for human target cells after incubation in mediator-rich supernates from antigen-stimulated lymphocytes. Maximum cytotoxicity was observed after 24-h incubation in mediators. In comparison to normal macrophages, mediator-activated macrophages were cytotoxic to five of the six malignant cell lines tested but had no effect on five nonmalignant cell lines. In 20 experiments with one target (SK-BR-3), mean cytotoxicity was 23 +/- 2.7% and with another target (MA-160), was 29 +/- 3.4%. Macrophages became cytotoxic after 8-h incubation with mediators and the enhanced cytotoxicity persisted for at least 40 h after the lymphocyte mediators were removed. These findings are consistent with the hypothesis that macrophages, activated by antigen-induced lymphocyte mediators, can contribute to the host resistance to tumor growth in man.

Cell Division↗
PubMed1979

Fibrin gel investment associated with line 1 and line 10 solid tumor growth, angiogenesis, and fibroplasia in guinea pigs. Role of cellular immunity, myofibroblasts, microvascular damage, and infarction in line 1 tumor regression.

Line 1 and line 10 tumors became invested in a fibrin-gel cocoon within hours after transplantation to the subcutaneous spaces of unsensitized syngeneic inbred Sewall Wright strain 2 guinea pigs. The fibrin gel comprised more than 80% of the line 1 tumor mass and, after day 3, became organized and was subsequently replaced by fibrous connective tissue, which gave the tumor the appearance of a scirrhous carcinoma. A cellular infiltrate of lymphocytes and basophils developed at the periphery of line 1 tumors after day 8, and tumors regressed by day 13. The fibrin gel investing the highly malignant line 10 tumors accounted for less than 10% of the tumor mass and persisted without fibrous organization as a tumor grew progressively and invaded adjacent tissues. These data provide new and potentially important insights into the biology of solid tumor growth and the mechanisms of immunologic tumor rejection. Envelopment of tumors in a fibrin gel created an anatomic barrier separating the tumors from the host. Neovascularization mimicking that about line 1 and line 10 tumors was induced by sc fibrin implants; these data suggest that activation of the clotting and/or fibrinolytic systems by tumor cells may itself provide sufficient stimulus for induction of tumor angiogenesis without requiring a separate tumor angiogenesis factor. The scirrhous pattern of growth characteristic of line 1 tumors apparently was achieved by organization of an abundant fibrin gel. Line 1 tumor regression did not for the most part involve direct contacts between tumor cells and any type of inflammatory cell, including macrophages; rather, tumor destruction was effected by ischemic necrosis secondary to widespread microvascular injury. The mechanisms of such injury are uncertain, but tumor rejection was correlated with evidence of developing cellular immunity and anatomic associations between lymphocytes and myofibroblasts. Further experiments will be necessary before these findings can be generalized to other tumor systems.

Animals↗
PubMed1979

Tumor-basophil interactions in vitro--a scanning and transmission electron microscopic study.

Purified guinea pig basophils, or basophils either specifically degranulated with antigen or nonspecifically degranulated with lectin, were cultured with guinea pig line 1 hepatoma cells for 1 to 24 hr and studied ultrastructurally. As early as 1 hr of culture, degranulated or nongranulated basophils and tumor cells formed close contacts by mutually intertwined elongated cell processes and also in cultures containing degranulated basophils, extruded membrane-free basophil cytoplasmic granules became firmly attached to tumor cells. At later intervals, some tumor cells cultured with basophils exhibited cytostatic and cytopathic changes, including dense mitochondria, centralization of organelles, dilated perinuclear and rough endoplasmic cisternae, cell swelling and cytoplasmic lucency, disrupted cytoplasmic organelle and plasma membranes, nuclear pyknosis and fragmentation. Some tumor cell specialized surface attachments were either disrupted or damaged at points of basophil or basophil granule adhesion. Tumor damage was most extensive in cultures containing degranulated basophils, although only a minority of tumor cells (less than 10%) was affected. Tumor injury was seen much less frequently in the presence of nondegranulated basophils, and was absent in control cultures of tumor alone. The occasional viable tumor cells that phagocytosed basophil granules were apparently unharmed, suggesting that internalization of basophil granules by tumor cells is not cytotoxic.

Animals↗
PubMed1978

Purification of human monocytes by continuous gradient sedimentation in ficoll.

A new method of obtaining purified human monocytes has been developed. The peripheral blood mononuclear leukocytes are isolated by centrifugation over Ficoll--Hypaque and then further purified by sedimentation over a linear 5--10% Ficoll density gradient. In ten experiments, the average purity obtained was 77.1% macrophages and the mean yield was 22.4% of the monocytes contained in the peripheral blood leukocytes. Viability of monocytes isolated by this technique exceeded 95%. The cells were phagocytic and responded to human migration inhibitory factor.

Blood Cell Count↗
PubMed1977

Immunologic abnormalities in patients with malignant lymphoproliferative diseases.

The B- and T-lymphocyte distribution was studied in 45 patients with malignant lymphoproliferative diseases. Eight patients with untreated Hodgkin's disease had normal mean percentages of complement receptor lymphocyte (CRL) cells and T-cells; however, the mean absolute number of T-cells was decreased. T-lymphocytes were also decreased in 3 patients with Hodgkin's disease treated 7-24 months previously. The number of T-lymphocytes increased markedly in all patients after treatment. Lymphocyte surface markers in non-Hodgkin's lymphoma showed distinctive patterns. Patients with leukemic reticuloendotheliosis or "hairy cell leukemia" characteristically had low percentages of CRL but normal or increased percentages of surface immunoglobulin-positive lymphocytes. The mean percentage and number of T-lymphocytes in this group were normal. Eight patients with nodular lymphocytic lymphoma and 2 patients with nodular lymphocytic-histiocytic lymphoma had normal mean numbers of CRL but decreased numbers of T-lymphocytes. Of 6 patients with diffuse lymphocytic lymphoma, 4 had elevated percentages and numbers of CRL. Despite low percentages, normal numbers of T-lymphocytes were found in 3 of these patients.

B-Lymphocytes↗
PubMed1977

Inhibition or enhancement of rat mammary tumors dependent on dose BCG.

The effect of BCG on the growth of transplantable rat mammary tumors in W/Fu rats was studied. Admixture of mycobacteria to tumor cells in vitro prior to their injection in vivo either had no effect on or resulted in inhibition of or enhancement of the growth of the tumor transplants. Inhibition occurred at high and enhancement at low mycobacteria:tumor cell ratios. However, following suppression of local tumor growth with high doses of BCG, the growth of a second tumor graft was enhanced. Pretreatment of rats with BCG alone also enhanced the growth of a subsequent tumor graft. These results suggest an inverse relationship between the optimal dose of BCG for suppression of local tumor and that required to induced systemic immunity.

Animals↗
PubMed1977

Transplantable mammary tumors in Wistar/Furth rats: development, antigenicity, and effect of hormone manipulations.

Transplantable tumor lines were developed from 7,12-dimethylbenz[a]anthracene-induced mammary tumors in inbred WF rats. Although the primary tumors regressed following oophorectomy, the growth of late generations of the transplantable lines was not affected by castration or by treatment with estrogens, androgens, and progesterone. This result coincided with a change in the morphology of the tumors from well-differentiated to poorly differentiated anaplastic tumors. The transplantable mammary tumors were antigenic in vitro as evidenced by stimulation of syngeneic lymphocytes in mixed lymphocyte-tumor cell cultures. However, prior sensitization by excision of a first tumor graft failed to protect the animals against a second challenge with cells from the same tumor line.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Multiple in vitro mechanisms of tumor cytotoxicity demonstrated in the line-1 guinea pig hepatoma model.

The line-1 guinea pig hepatoma was used to study in vitro tumor cytotoxicity. Cytotoxicity was determined by measurement of the loss of tritiated thymidine-labeled target cells from culture vessels. With this technique, we demonstrated that significant tumor cytotoxicity was caused by lymphoid cells from tumor-immune guinea pigs, by cells from guinea pigs immunized against an antigen urelated to the tumor target, and by cell-free supernatants rich in lymphocyte mediators. Addition of normal peritoneal exudate cells enhanced the cytotoxic potential of a small number of highly purified immune lymphocytes, which suggested that recruitment of normal cells is an additional mechanism of tumor cell death in this system.

Animals↗
PubMed1975

Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells.

Normal guinea pig macrophages incubated for 3 days in vitro with mediator-rich lymphocyte supernatants become cytotoxic for the syngeneic tumors, line 1 hepatoma and MCA-25 fibrosarcoma. Under identical experimental conditions the survival of two normal syngeneic cell types, fibroblasts and kidney cells, was not affected. The activating supernatants were prepared by stimulating sensitized lymphocyte cultures with an antigen unrelated to the target cells. Therefore, this type of macrophage-mediated cytotoxicity appears to be nonspecific but restricted to cells with malignant growth capacities.

Ascitic Fluid↗
PubMed1975

Specificity of basophils and lymphocytes in cutaneous basophil hypersensitivity.

Using a rosetting technique, it was found that the vast majority of basophils circulating in the blood or accumulating in the skin reactions of guinea pigs primed for cutaneous basophil hypersensitivity (CBH) lacked demonstrable specificity for sensitizing antigen, whether sheep erythrocytes, a soluble protein, or tumor cells. By contrast, one-third of cells teased from late skin reactions formed specific rosettes as did nearly 80% of circulating basophils in animals receiving repeated doses of whole sheep blood. Unreactive basophils teased from CBH reactions readily acquired rosetting capacity on exposure to immune serum. With regard to lymphocyte (and hence reaction) specificity, both CBH and classic delayed hypersensitivity (DH) reactions exhibited a high degree of carrier specificity when dinitrophenyl-conjugates were used. Thus, in the hapten-carrier combinations examined thus far, the antigen skin test requirements for both CBH and DH have been identical and are those required for inducing an active lymphocyte response. These findings indicate that control mechanisms other than homocytotropic antibodies must be sought to explain the accumulation and behavior of basophils in CBH reactions and, coupled with other data, suggest that lymphocytes and/or their products are likely candidates for this role.

Animals↗
PubMed1975

Macrophages activated as suspension cultures with lymphocyte mediators devoid of antigen become cytotoxic for tumor cells.

Normal peritoneal exudate cells (PEC) were activated as suspension cultures either in mediator-rich supernatants from o-chlorobenzoyl-bovine gamma-globulin (OCB-BGG) stimulated lymphocytes or in antigen-free Sephadex fractions from these supernants. After 24 hr incubation thration. The adherent cell fractions of PEC, recovered by trypsinization from monolayers and activated by this technique, were as cytotoxic as unfractionated PEC. Lymphocyte supernatants and antigen-free fractions of the supernatants induced comparable macrophage-mediated tumor cytotoxicity. Treatment of activated macrophages with trypsin did not alter their cytotoxic capacity.

Animals↗