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Accidental overdose of multiple chemotherapeutic agents.

A 35-year-old man with refractory low grade diffuse centroblastic centrocytic non-Hodgkin's lymphoma was treated accidentally with an overdose of multiple chemotherapeutic agents. He was given adriamycin 50 mg/m2 and cyclophosphamide 350 mg/m2 for 6 days followed by 4 days of vincristine 1 mg/m2 and bleomycin 10 mg/m2. He was transferred when he developed pancytopenia, fever, severe mucositis, ileus and peripheral neuropathy. He was treated with broad spectrum antibiotics, red cell and single donor platelet transfusions and strict parenteral nutrition. In addition, he was given a continuous infusion of 400 micrograms daily human recombinant granulocyte macrophage-colony stimulating factor (rh GM-CSF) for 17 days. Intractable severe bleeding from his oral mucositis necessitated treatment with a continuous infusion of 8-ornithine-vasopressin for 8 days. He recovered and could be discharged home after 36 days of hospitalization with normal blood counts and without severe sequelae.

Adult↗

[Factors related to the olive size in patients with hypertrophic pyloric stenosis].

INTRODUCTION: The pyloric "olive" (PO) is the result of the anomalous growth of the pyloric muscle among patients with pyloric stenosis (PS). It frequently is unexpectedly large, or some other times surprisingly small, and those variations in size have been difficult to explain. MATERIALS AND METHODS: We measured the PO in 145 consecutive patients with PS during the operation, and then we classified them as small if their length was less than 20 mm, medium if 20 to 30 mm, or large if more than 30 mm; several variables were analyzed by mean of the chi square or Spearman rho tests. RESULTS: Six cases were excluded due to an unclear total length record of the PO. The PO size was classified as small in 19 (13.7%), medium in 71 (51%) and large in 49 (35.3%). The PO size did not associate with gender, way of birth, the presence of jaundice, constipation or any specific blood group or Rh factor, and it did not correlate with birth weight or month and gestational order either. Medium and large PO were more frequently palpated than smaller (94-100% vs. 83%, p = 0.009); PO size correlated with the duration of the history of vomiting (CQ 0.267, p = 0.002), child's age (CQ 0.243, p = 0.005) and weight at operation (CQ 0.190, p = 0.048). A daily weight loss surpassing 5 g was more commonly found among small PO (p = 0.038). CONCLUSIONS: In more than a third of the PS patients, PO is unexpectedly large, and in one of every seven it is surprisingly small. The bigger PO size associates with a longer disease, and with older and heavier patients, which probably is explained by a slighter clinical course. A small PO is more difficult to palpate during clinical evaluation.

Female↗

Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts.

As part of a broad phase I study of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF), four patients were treated who had myelodysplastic syndrome (MDS) with excess blasts. The GM-CSF was given daily as an intravenous injection over a period of 30 min for 5 days. A total of 11 cycles were conducted. Each patient received at least two different dose levels. In three patients, three different dosages were delivered. The treatment course was interrupted by a 10-day rest period. Rh GM-CSF was well tolerated, with only minor side effects seen, which included bone discomfort at the lower back, sternum and ribs, and constitutional symptoms such as low grade fever, nausea/vomiting, and mild myalgias. Whereas no increases in platelet and reticulocyte counts were recorded, elevations of absolute neutrophil counts above 100 cells/microliters occurred in all patients. The most striking finding was, however, the development of increases in the number of circulating and bone marrow blast counts that were observed particularly when doses of greater than or equal to 500 micrograms/m2 of body surface area were administered. In line with data demonstrating in vitro induction of proliferation of leukemic blast cells by rh GM-CSF, one may take advantage of blastogenesis induced in vivo that may favor the use of a therapeutic strategy by recruiting quiescent cells into the mitotic cycle which would then represent optimum targets for a subsequent cycle-specific cytotoxic chemotherapy. Such an approach could form the basis for new clinical trials in MDS.

Adult↗

Human fibroblasts maintain the viability and augment the functional response of human neutrophils in culture.

When human neutrophils were co-cultured for 72 h with nontransformed human fibroblasts, 69 +/- 3% (n = 13) survived, as compared with survival levels of 2 +/- 1% (n = 15) and 26 +/- 6% (n = 7), respectively, for neutrophils cultured for the same time period in enriched medium alone or supplemented with 10 pM recombinant human granulocyte/macrophage colony-stimulating factor (rh GM-CSF). Conditioned medium from the human fibroblast cultures enhanced neutrophil survival in a dose-dependent fashion to the same level achieved with neutrophil/fibroblast co-cultures, and its soluble viability-sustaining activity was not inhibited by preincubation with neutralizing antiserum against rh GM-CSF. As compared with freshly isolated replicate samples, neutrophils co-cultured with human fibroblasts for 72 h exhibited augmented FMLP-stimulated superoxide production without spontaneous superoxide generation. This striking extension of survival and associated priming for a ligand response by neutrophils co-cultured with human fibroblasts suggests that fibroblasts may contribute to the proinflammatory properties of neutrophils in tissues.

Cell Survival↗

Interleukin-6 stimulates cell proliferation of rat pituitary clonal cell lines in vitro.

We investigated the effect of recombinant human IL-6 (rhIL-6) on cell proliferation using the MtT/E rat pituitary tumor cell line, which was recently established by Inoue et al. This cell line expresses the homeodomain protein Pit-1/GHF 1 and does not produce any significant amount of pituitary hormones, but retains its tumorigenicity by back-transplantation into rats, resulting in production of prolactin. MtT/E cells were seeded into Falcon 24-well plates at a density of 2 x 10(4) cells/well in a cultured medium, containing 10% horse serum and 2.5% fetal bovine, with test drug. After four-days (12 days for the time-course study) incubations, the cells were counted using a hemocytometer. Incubation for 4 days with rhIL-6 caused concentration-dependent stimulation of MtT/E cell growth and [3H]-thymidine incorporation into MtT/E cells. Addition of 20 ng/ml rhIL-6 to the culture medium stimulated MtT/E cell growth in a time-dependent manner, withdrawal of rhIL-6 from the culture medium reduced MtT/E cell growth, and re-addition of rhIL-6 to the culture medium again stimulated MtT/E cell growth. Among the cytokines tested, granulocyte colony-stimulating factor (rh G-CSF) also showed a slight but significant mitogenic activity on the MtT/E cells. Analysis of 125I-rhIL-6 binding to the MtT/E cells indicated a dissociation constant of 0.953 x 10(-9) mmol/l and the presence of 968 binding sites per cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The groupamatic system for routine immunohematology.

Approximately 6000,000 routine immunohematological tests have been conducted with Groupamatic GC systems at the National Blood Transfusion Center in Paris. The system is used for determination of the ABO group including A1 and A2 subgrouping; the Rh factors including Du, C, c, E, e, CW;K;Lea; P1; M and N. The detection and identification of irregular alloantibodies is carried out systematically together with detection of the anti-A and anti-B antibodies. Simultaneously, testing for syphilis is done with a cardiolipid antigen. Groupamatic equipment allows 340 samples to be tested per hour and 12 reactions can be carried out simultaneously on each sample. The system is fully automated.

ABO Blood-Group System↗

Blood group distribution in women with ovarian cancer.

The distribution of ABO blood groups and Rh factor was studied in 1930 patients treated at Radiumhemmet for ovarian tumour in the period 1958-1973. The tumour was malignant in 1732 cases and of borderline malignancy in 198. A predominance of blood group A at the expense of group O emerged when the series was compared with findings in 24 120 healthy conscripts. In the present series, the disparity between the frequencies of blood groups A and O appeared to increase the risk of ovarian carcinoma by 19%. The frequencies of blood groups among various histological subgroups are discussed.

Epidemiologic Methods↗

Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts.

Normodense human peripheral blood eosinophils were isolated under sterile conditions from the 22/23 and 23/24% interfaces and the cell pellet of metrizamide gradients. After culture for 7 d in RPMI media in the presence of 50 pM biosynthetic (recombinant) human granulocyte/macrophage colony-stimulating factor (rH GM-CSF), 43 +/- 7% (mean +/- SEM, n = 8) of the cells were viable; in the absence of rH GM-CSF, no eosinophils survived. The rH GM-CSF-mediated viability was concentration dependent; increased survival began at a concentration of 1 pM, a 50% maximal response was attained at approximately 3 pM, and a maximal effect was reached at concentrations of greater than or equal to 10 pM rH GM-CSF. In the presence of rH GM-CSF and mouse 3T3 fibroblasts, 67 +/- 6% (mean +/- SEM, n = 8) of the eosinophils survived for 7 d. In a comparative analysis, there was no difference in eosinophil viability after 7 and 14 d (n = 3) in the presence of 50 pM GM-CSF and fibroblasts. Culture with fibroblasts alone did not support eosinophil survival. The addition of fibroblast-conditioned media to rH GM-CSF did not further improve eosinophil viability, indicating a primary role for GM-CSF in supporting these eosinophil cell suspensions ex vivo and a supplementary role for 3T3 fibroblasts. Eosinophils cultured for 7 d localized on density gradient sedimentation at the medium/18, 18/20, and 20/21 interfaces of metrizamide gradients, indicating a change to the hypodense phenotype from their original normodense condition. In addition, the cultured eosinophils generated approximately 2.5-fold more LTC4 than freshly isolated cells when stimulated with the calcium ionophore A23187 and manifested sevenfold greater antibody-dependent killing of S. mansoni larvae than the freshly isolated, normodense cells from the same donor. Thus we demonstrate the rH GM-CSF dependent conversion in vitro of normodense human eosinophils to hypodense cells possessing the augmented biochemical and biological properties characteristic of the hypodense eosinophils associated with a variety of hypereosinophilic syndromes. In addition, these studies provide a culture model of at least 14 d suitable for the further characterization of hypodense eosinophils.

Animals↗

[Usefulness of intraperitoneal transfusion under direct ultrasound guidance].

Experience with intraperitoneal blood transfusion, using ultrasonographic guide, in 24 patients with severe isoimmunization to Rh factor, is reported. A total of 57 procedures, were done from 24 weeks of gestation. In 66.6% two or more transfusions were done in the same product. There were 71% of alive newborns and in 29% of the cases it was not possible to improve perinatal survival. The analysis of these results were correlated with antecedents: presence of hydrops, gestational age at the time of resolving pregnancy, and main disease status. The usefulness of intraperitoneal transfusion, is commented upon, and new perspectives, as intravascular transfusion in cases with severe hydrops, are considered.

Blood Transfusion, Intrauterine↗

Examination of the role of the proteolytically-activated form of protein kinase C in the differentiation of human haemopoietic cells.

In neutrophils, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the translocation of the Ca(++)- and phospholipid-dependent protein kinase, protein kinase C (PK-C) from the soluble to the particulate fraction. At the same time there was a corresponding increase in the amount of Ca(++)- and phospholipid-independent protein kinase activity recovered in the soluble fraction. This soluble Ca(++)- and phospholipid-independent protein kinase presumably reflects proteolytic activation of the particulate associated PK-C. Bone marrow and undifferentiated HL-60 cells also translocated PK-C to the particulate fraction in response to TPA but did not accumulate the soluble Ca(++)- and phospholipid-independent form of the enzyme. Similar results were obtained using HL-60 cells induced to differentiate with dimethyl sulphoxide (DMSO), recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) or 1 alpha,25-dihydroxyvitamin D3. There was also no significant change in either the number or time of expression of differentiation-specific cell surface antigens observed on HL-60 cells induced to differentiate with either DMSO, 1 alpha,25-dihydroxyvitamin D3 or TPA in the presence of cyclosporin A, an agent reported to inhibit the proteolytic breakdown of PK-C to the Ca(++)- and phospholipid-independent form. Likewise, cyclosporin A did not affect the rate of extent of differentiation of primary bone marrow cell cultures. These results suggest that the proteolytically activated and phospholipid-independent form of PK-C is probably not involved in haemopoietic cell differentiation.

Biological Transport↗

Spontaneous remission of granulocyte colony-stimulating factor-associated leukemia in a child with severe congenital neutropenia.

Leukemia is observed with increased frequency in patients with severe congenital neutropenia (SCN). In the past decade, recombinant human granulocyte colony-stimulating factor (rh G-CSF) has prolonged the survival of patients with SCN increasingly reported to have leukemias. In this communication acute myelogenous leukemia (AML) associated with a mutation of the G-CSF receptor (G-CSF-R) developed in a patient with SCN maintained on long-term G-CSF therapy. The blast count in the blood and bone marrow fell to undetectable levels twice on withholding G-CSF and without chemotherapy administration, but the mutant G-CSF-R was detectable during this period. The patient subsequently underwent successful allogeneic bone marrow transplantation. After transplantation, the patient's neutrophil elastase (ELA-2) mutation and G-CSF-R mutation became undetectable by polymerase chain reaction. This report provides novel insights on leukemia developing in congenital neutropenia.

Bone Marrow Transplantation↗

Functional role of dendritic cells in patients with unstable angina.

To investigate the function of dendritic cells (DC) in patients with unstable angina, 10 mL of blood was drawn from 30 subjects. 15 patients diagnosed as having unstable angina and 15 healthy subjects were included in an observation and a control groups respectively. The mononuclear cells were separated from the peripheral blood and cultured in RPM11640 supplemented with recombinant human granulocyte/macrophage-colony stimulating factor (rh GM-CSF) and recombinant human interleukin-4 (rh IL-4) to induce dendritic cells. The shape and ultrastructure of DC was examined with electronic microscope. The phenotype of DC was analyzed with FACS and the alloantigen presenting capacity of DC was evaluated by mixed lymphocyte reaction (MLR). The expression rate of CD86 of DC in patients with unstable angina was (40.7 +/- 3.6) %, which was obviously higher than that of normal DC (29.6 +/- 2.5%) ( P < 0.001). The capacity of the DCs in unstable angina patients to induce allogenic T cells (OD 2.73 +/- 1.10), was significantly higher than that of the normal DC (OD:0.9 +/- 0.21) (P < 0.005). It is suggested that the function of DC in patients with unstable angina is increased, which may play an important role in the initiation of immune reaction in the plaque.

Adult↗

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.

Adolescent↗

Transplantation of G-CSF mobilized allogeneic peripheral blood stem cells in rabbits.

Mobilized peripheral blood precursor cells (PBPC) are used with increasing frequency to restore autologous hematopoiesis following high-dose radio-chemotherapy. The success of this method has aroused interest in the use of mobilized PBPC for allogeneic transplants. This approach would eliminate the need for marrow aspiration and general anesthesia. In this project we tested the feasibility of allogeneic histoincompatible PBPC transplants in rabbits. Adult outbred Red Burgundy rabbits were used as donors, histoincompatible New Zealand White rabbits of the opposite sex as recipients. One individual donor was used for one individual recipient. Conditioning consisted of 10 Gy total body irradiation (TBI). Donor animals were pre-treated with recombinant human granulocyte colony-stimulating factor (rh G-CSF) given s.c. at 10 micrograms/kg daily. Three schedules of PBPC collection and reinfusion were tested in 3 groups of animals, each consisting of 5 donor recipient pairs: (A) PBPC were collected either on days -2, -1 and 0, and infused at once after TBI on day 0; (B) collected and infused on days 0, +2, +4, +7, +9, and +11; (C) collected on 3 consecutive days, cryopreserved for 1 month and infused on day 0 followed by 3 fresh donations on days +4, +8 and +11. The median amount of blood processed from donor animals was 470 ml (312-602) containing about 10 x 10(8) (5-71 x 10(8)) nucleated cells. Recipient animals received a median of 2.7 x 10(8) cells/kg equivalent to 9.6 x 10(4) colony-forming units granulocyte-macrophages (CFU-GM)/kg (data derived from Group C of the animals).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Action of granulocyte-colony stimulating factor and cisplatin on two models of human digestive, esophageal and colonic, cancers].

A combined therapy using a colony-stimulating factor and a chemotherapeutic agent has been designed, in vitro and in vivo, on digestive tumor cells to assess the effects of these agents administered alone or in combination, on the cells' or the tumor's growth rate. A recombinant human granulocyte colony-stimulating factor (rh G-CSF) and Cisplatin (CDDP) has been administered at various concentrations in vitro on oesophageal (ECYO) or on colonic (COLO 205) cell lines and in vivo on oesophagal tumor transplanted in Nude mice. In vitro, the oesophagal model is sensitive to G-CSF. The administration of G-CSF induces a stimulation of the cell proliferation. The DNA synthesis is stimulated or inhibited by low or high concentrations of G-CSF without any dose-response relationship. CDDP inhibits the DNA synthesis in ECYO cells. The association of the two agents leads to an activation of the DNA synthesis but only for some concentrations. On the contrary, the colonic model treated or not by CDDP is not sensitive to G-CSF. In vivo, G-CSF does not allow any inhibition or activation of oesophagal tumor's growth rate. CDDP alone is also inefficient. When G-CSF is administered before CDDP, there is no effect on the tumors. On the contrary, when G-CSF is administered with or after the chemotherapeutic agent, there is a significant inhibition of the tumor's growth rate.

Animals↗

Biology of Saryupari Brahmins of Chhattisgarh, central India.

In July-November, 1986, Saryupari Brahmins of Chhattisgarh (Central India) have been investigated for the distribution of ABO blood groups, Rh factor, ABH secretion, PTC taste sensitivity and seven morphological traits. The important findings in brief are as follows: 1. The frequency of O blood group is slightly dominant (38.91%) and gene frequency exhibit r > q > p pattern. Statistical analysis (D/sigma = 0.5447) show that the population is in genetic equilibrium. 2. Estimation of the expected rate of erythroblastosis foetalis occurred in this population is calculated to be 8-16 cases in every 10,000 pregnancies. 3. High incidence (53.82%) of non-secretors of ABH substances in saliva suggest that this group may belong to Caucasoid stock. 4. The ability to taste the chemical PTC has a high frequency (61.81%) in this group. 5. R/L type of handclasping (58.15%), leg folding (65.38%) and L/R type of arm folding (58.93%) is dominant. L-type of handedness (5.48%) is moderately high. 6. Tongue rollers (93.28%) and folders (53.77%) are more among them. 7. Free type of ear lobe (68.68%) is the common feature in this population. 8. The above observations were compared in details with other Brahmin populations reported from India with special reference to the descendant groups residing in Madhya Pradesh (Central India). Furthermore, the results obtained on growth studies, and dermatoglyphic studies (palm and sole) from our published literature were also included so as to have some idea on the genetical, behavioural, dermatoglyphic and growth norms of this group.

ABO Blood-Group System↗

A linkage study of manic-depressive disorder with HLA antigens, blood groups, serum proteins and red cell enzymes.

Families with a two-generational history of affective disorder and well and ill sibs were selected from a population of bipolar manic-depressive patients and typed for HLA antigens, blood groups, serum proteins and red cell enzymes. Segregation of specific HLA alleles was not associated with affective illness across family pedigrees. Further, no significant associations were found between affective disorder and ABO, Rh, MNSs blood groups or Hp, EsD, C3, Gc or PGM. Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.

Adolescent↗