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PubMed1989

GM-CSF accelerates neutrophil recovery after autologous bone marrow transplantation for Hodgkin's disease.

Thirty-one patients with resistant Hodgkin's disease were treated by an identical high dose chemotherapy regimen and autologous bone marrow transplantation. Twelve of these patients received recombinant human granulocyte/macrophage colony stimulating factor (rh GM-CSF) in a phase I/II study. rh GM-CSF was administered by continuous infusion into an indwelling central venous catheter for 3-21 days at doses of 100-400 micrograms/m2/day. The patients receiving rh GM-CSF did not differ significantly from those who did not receive growth factor with regard to age, previous therapy or number of bone marrow cells infused. rh GM-CSF resulted in more rapid neutrophil regeneration, the average time to achieve a neutrophil count of greater than or equal to 0.5 x 10(9)/l being 17.5 days compared to 24.9 days in the control group (p less than 0.01). Platelet recovery was very varied and not accelerated by rh GM-CSF. Patients receiving rh GM-CSF had a similar infection rate (58% vs 68% in the control group), similar number of febrile days (5.0 vs 4.7 days) and similar period of hospitalization to the control group (30.1 vs 30.2 days). Randomized controlled trials are now required to define the clinical value of rh GM-CSF in the setting of autologous bone marrow transplantation.

Agranulocytosis↗
PubMed1997

Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group.

OBJECTIVE: Our goal was to identify risk factors for the development of preeclampsia in nulliparous women enrolled in a multicenter trial comparing calcium supplementation to a placebo. STUDY DESIGN: A total of 4589 women from five centers was studied. Analysis of risk factors for preeclampsia was performed in 4314 who carried the pregnancy to > 20 weeks. Baseline systolic and diastolic blood pressure, demographic characteristics, and findings after randomization were examined for the prediction of preeclampsia. Preeclampsia was defined as hypertension (diastolic blood pressure > or = 90 mm Hg on two occasions 4 hours to 1 week apart) and proteinuria (> or = 300 mg/24 hours, a protein/creatinine ratio > or = 0.35, one dipstick measurement > or = 2+ or two dipstick measurements > or = 1+ at an interval as specified for diastolic blood pressure). RESULTS: Preeclampsia developed in 326 women (7.6%). The first analysis treated each risk factor as a categoric variable in a univariate regression. Maternal age, blood group and Rh factor, alcohol use, previous abortion or miscarriage, private insurance, and calcium supplementation were not statistically significant. Risk factors initially found to be significant were body mass index, systolic blood pressure, diastolic blood pressure, non-white race (African-American and other), clinical center, and smoking. Adjusted odds ratios computed with a logistic regression model revealed that body mass index (odds ratio 3.22 for > or = 35 kg/m2 vs < 19.8 kg/m2), systolic blood pressure (odds ratio 2.66 for > or = 120 vs < 101 mm Hg), diastolic blood pressure (odds ratio 1.72 for > or = 61 mm Hg vs < 60 mm Hg), and clinical center (odds ratio 1.85 for Memphis vs the other clinical centers) were statistically significant predictors of preeclampsia. Results of the final model fit revealed that preeclampsia risk increases significantly (p < 0.0001) with increased body mass index at randomization, as well as with increased systolic and diastolic blood pressure at randomization. Calcium supplementation had no effect on the risks posed by body mass index and blood pressure. Among risk factors developing after randomization, an abnormal results of a glucose screen (plasma glucose > or = 140 mg/dl 1 hour after a 50 gm glucose challenge) was not found to be associated with a significant risk of preeclampsia. CONCLUSION: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.

Adolescent↗
PubMedDate not supplied

Effect of in vivo treatment with rh GM-CSF on in vitro growth of haematopoietic progenitors in patients with myelodysplastic syndromes.

BACKGROUND: Recombinant (r) human (h) granulocyte/macrophage colony stimulating factor (rh GM-CSF) has been shown to increase the number of peripheral blood (PB) neutrophils, eosinophils and monocytes in myelodysplastic syndromes (MDS). The aims of this study were: 1) to evaluate the effect of rh GM-CSF therapy on the in vitro growth of granulocyte-erythroid-macrophage-megakaryocyte colonies (CFU-GEMM), erythroid colonies (BFU-E), and granulocyte-macrophage colonies (CFU-GM) in patients with MDS; 2) to assess in these patients, while they are being treated in vivo with rh GM-CSF, the possible additive effect of rh IL-3 and rh G-CSF on the in vitro growth of haematopoietic progenitors. METHODS: The in vitro growth of CFU-GEMM, BFU-E and CFU-GM was studies in 10 myelodysplastic (MDS) patients, before and after in vivo administration of rh GM-CSF. RESULTS: After rh GM-CSF administration, the number of CFU-GM increased in all standard risk MDS patients. In 2 out of 5 cases, this effect was more pronounced and persisted up to 30 days after the end of rh GM-CSF treatment. On the other hand, the number of CFU-GEMM and BFU-E was substantially unchanged. When rh GM-CSF, rh G-CSF and rh IL-3 were added in vitro alone or in combination as the source of colony stimulating activity, no significant increase of the CFU-GM colony number was noticed. CONCLUSIONS: Rh GM-CSF therapy appears useful for increasing the number of peripheral blood granulocytes and of marrow CFU-GM in standard-risk MDS patients. High-risk MDS patients are far less responsive to rh GM-CSF treatment, probably reflecting a more aggressive and/or advanced disease.

Colony-Forming Units Assay↗
PubMed1986

Haptoglobin type in connection with mean age at first breast cancer signs?

In breast cancer patients divided into groups according to haptoglobin (Hp) type (519 patients), blood group (ABO) (433 patients) or Rh factor (358 patients) the mean age at first disease manifestation was calculated. The results indicate that in Hp 1 bearers breast cancer appears at significantly lower age (49 years) as compared to Hp type 2-1 (53.3 years) or Hp 2 (53 years). In blood groups the mean age at first cancer signs raises from 48 years in the AB group to 53.1 years in the A group, only the difference between A and AB being significant. However, these preliminary results require confirmation in larger patient series.

ABO Blood-Group System↗
PubMed1975

[Pre- and postnatal treatment of severe Rh-erythroblastosis (author's transl)].

162 children with severe Rh-erythroblastosis were treated with 326 prenatal blood transfusions. 89 (55%) survived. The indication and technique for this treatment and the postnatal intensive care of the newborn are reported. Prenatal diagnosis is extended by the author's immunofluorescence technique assessing the fetal Rh factor D even as minute contamination amongst other cells, in order to privente unnecessary treatment of Rh negative children. Checking the effectiveness of prenatal blood-transfusion this technique can demonstrate differences in the counts of HbF- and D-cells. Success of treatment appears to be, in part, determined by dexamethasone just before delivery and by immediate postnatal substitution of erythrocyte concentrates and following exchange transfusion. With increasing experience the percentage of successful treatment rose. Of 40 children treated during the last 2 years with 95 prenatal transfusions, 67,5% survived. 41 fetuses had ascites already at the first prenatal transfusion. 9 of them (22%) survived. The data of the children treated, earliest in the 21st week of pregnancy, are given: Bilirubin level in amniotic fluid, number of prenatal transfusions, gestational week at delivery, hematocrit, HbF cells, number of postnatal exchange transfusions and later transfusions. Postnatal development of successfully treated children corresponds to that of other premature children without erythroblastosis.

Amniotic Fluid↗
PubMed1979

[ABO system blood groups and the rhesus factor in tumors and tumorlike processes of the ovaries].

Under observation were 175 patients with ovarian tumors and cysts. The distribution of ABO blood groups and Rh factor in relation to this pathology was studied as compared with the control series (2000 healthy females). There was noted an increased probability of the incidence of the majority of the ovarian tumor types among AB blood group females compared with other groups (O, A and B), and just the opposite, the probability of the tumoriform processes incidence in AB group females is considerably less than in other groups. The probability of ovarian tumors malignification proved to be the least in B group females. There is noted a considerably increased relative ovarian tumor and cyst morbidity among Rh-positive females compared with Rh-negative ones.

ABO Blood-Group System↗
PubMed1987

Preclinical approaches to the treatment of metastatic disease: therapeutic properties of rH TNF, rM IFN-gamma, and rH IL-2.

The present studies were undertaken to examine the immunotherapeutic properties of recombinant murine interferon-gamma (rM IFN-gamma), recombinant human tumour necrosis factor (rH TNF), and recombinant human interleukin-2 (rH IL-2) in preclinical metastasis models. It was observed that these cytokines have disparate mechanisms of therapeutic activity as well as different optimal therapeutic protocols. Thus, not only is the dose important to the therapeutic activity of each of the agents; so also is the route of administration, schedule of administration, duration of administration, and sequence of administration. The rM IFN-gamma has a narrow window of activity, with a bell-shaped therapeutic response with a dosage optimum at 50,000 U/animal of rM IFN-gamma administered 3 times per week. In contrast, rH IL-2 has optimal therapeutic activity for the treatment of metastatic disease after i.p. as compared to i.v. administration. This appears to be associated with the serum pharmacokinetics, since longer serum concentrations are achieved following i.p. administration although lower serum levels are also achieved. RH IL-2 has a biphasic dose-response curve for therapeutic activity with optima from 100 to 1000 U/animal and at doses greater than 100,000 U/animal. The lower doses appear to be associated with T cell augmentation whereas the higher doses are associated with NK cell or LAK cell augmentation. RH TNF has therapeutic activity for the treatment of metastatic disease after i.v. but not i.p. administration. High levels of rH TNF are readily detected in the serum following i.v. administration, with a serum half-life of approximately 30 min. In contrast, only minimal serum TNF activity is observed after i.p. administration, suggesting that this may be the origin of the increased therapeutic activity following i.v. administration. Furthermore, rH TNF has additive therapeutic activity when administered in conjunction with suboptimal doses of rM IFN-gamma. Unfortunately, the additive therapeutic activity of rM IFN-gamma and rH TNF is also associated with increased toxicity. However, in preliminary experiments it was found that the b.i.d. administration of aspirin at 25 mg/kg resulted in decreased toxicity. In summary, the recombinant cytokines provide a challenge both preclinically and clinically to the development of optimal therapeutic protocols, and suggest that close attention must be paid to the dose, route, schedule, duration, and sequence of their administration.

Animals↗
PubMed1991

Recombinant human interleukin 3 induces proliferation of inflammatory cells and keratinocytes in vivo.

In this preclinical study we investigated the effect(s) of recombinant human (rh) interleukin 3 (IL-3) on hemopoietic differentiation and attempted to evaluate possible clinical side effects of this hemopoietic growth factor. Rh IL-3, derived from either Escherichia coli or Chinese hamster ovary, was administered subcutaneously to 16 rhesus monkeys (by pairs) at different doses (11, 33, and 100 micrograms/kg/day) for 14 days. During the 2nd week of administration white blood cell counts increased 2- to 3-fold mainly because of a dose-dependent elevation of basophils (up to 40% of white blood cells) and eosinophils. In addition, moderate to marked elevations of plasma histamine levels were measured. Transient diarrhea and an erythematous skin rash with generalized cutaneous lesions that was not restricted to the injection sites were present in 3 of 6 animals treated with E. coli-derived rh IL-3 (1 of 2 animals that received 33 micrograms/kg and 2 of 2 that received 100 micrograms/kg) and 2 of 6 monkeys treated with Chinese hamster ovary-derived rh IL-3 (1 of 2 that received 33 micrograms/kg and 1 of 2 that received 100 micrograms/kg), respectively. Histopathologic and immunohistologic evaluation of skin specimens revealed a perivascular mononuclear cell infiltrate interspersed with numerous mast cells. Signs of vasculitis were absent. The density of the perivascular infiltrate correlated not only with the dose of IL-3 but also with the duration of the skin eruption. Moreover, hyperproliferation of basal keratinocytes resulting in acanthosis was observed in lesions persisting for 1 and 4 days as also evidenced by a significant (p less than 0.01) increase in Ki-67 (a proliferation-associated marker)-positive basal keratinocytes.

Animals↗
PubMedDate not supplied

Prevalence of blood groups in tribals of South Sudan.

Prevalence of ABO blood groups and Rhesus-factor in Southern Sudanese is shown in the Study. 42.81% were group A. group AB was the least common. Only 0.47% were negative for RH-factor.

Blood Group Antigens↗
PubMed1997

Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha.

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.

Animals↗
PubMed1996

ABO blood groups and salivary gland tumors (Alabama, United States).

Studies of associations between various diseases and the ABO blood groups have shown elevated relative risks for some categories of disease. A strong association between salivary gland tumors and blood group A has been reported, but studies are few and have yielded contradictory results. To investigate this association, we conducted an epidemiologic study of salivary gland tumors diagnosed in Jefferson Country, Alabama (United States), 1968-89. All tumors were histologically confirmed. Blood group information was obtained for 200 individuals with salivary gland tumors, and the distribution of ABO and Rh blood type for cases was compared with that of 52,118 healthy blood donors from the same geographic area. The 38.5 percent of salivary gland tumors in cases with blood group A was similar to the 39.0 percent observed for controls (P = 0.95). No differences were observed when benign and malignant tumors were considered separately, nor for any of the major histologic types of tumor. The distribution of Rh factor among cases and controls also did not differ significantly (P = 0.08).

ABO Blood-Group System↗
PubMedDate not supplied

[Amniotic fluid, amniocentesis, postmaturity].

The exchange among the elements of amniotic liquid is a dinamic process which keeps stable the concentration of their components, showing a variable relation with the maternal plasma in the differents stages of gestation. Thus the formations of the kidneys modifies the amniotic liquid with the urine excretion and then, factors as swallowing; the secretions of the skin and bronchi are factors which are implicated in its production. The amniocentesis is important in the study of high risk fetus, particulary with a prognostic value in the pregnancy sensitized to the Rh factor. The non cultivated celle give us information about the sexual chromatine and enzymes, to get a quick diagnosis, but this has to be confirmed with a culture cells for a final diagnosis, especially in diseases caused by inborn errors of metabolism.

Amniocentesis↗
PubMed1984

ABO-blood groups and D-antigen in simple and capsular glaucoma.

ABO-blood groups and Rh-factor (D-antigen) were determined in 236 patients with POAG, 104 simple and 132 capsular glaucoma. There was a statistical significant difference in the ABO-distribution between the two glaucoma subgroups, and also between the capsular-group and our control material. The simplex-group did not differ from the control material in this respect. For the Rh-group (D-antigen) no differences were found, neither between the two glaucoma subgroups nor between each of them and a reference material.

ABO Blood-Group System↗
PubMed1986

Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival.

A purified recombinant human granulocyte-macrophage colony stimulating factor (rH GM-CSF) was a powerful stimulator of mature human eosinophils and neutrophils. The purified rH GM-CSF enhanced the cytotoxic activity of neutrophils and eosinophils against antibody-coated targets, stimulated phagocytosis of serum-opsonized yeast by both cell types in a dose-dependent manner, and stimulated neutrophil-mediated iodination in the presence of zymosan. In addition, rH GM-CSF enhanced N-formylmethionylleucylphenylalanine(FMLP)-stimulated degranulation of Cytochalasin B pretreated neutrophils and FMLP-stimulated superoxide production. In contrast, rH GM-CSF did not promote adherence of granulocytes to endothelial cells or plastic surfaces. rH GM-CSF selectively enhanced the surface expression of granulocyte functional antigens 1 and 2, and the Mo1 antigen. rH GM-CSF induced morphological changes and enhanced the survival of both neutrophils and eosinophils by 6 and 9 h, respectively. These experiments show that granulocyte-macrophage colony stimulating factor can selectively stimulate mature granulocyte function.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1993

Clinicopathologic correlations of ABO and Rhesus blood type in colorectal cancer.

There is no specific association established between colorectal cancer and blood group type. In this study, the distribution of ABO and Rh blood groups was studied in 838 patients with colorectal cancer. There was no difference in distribution of ABO blood groups between patients who were Rh+ and Rh-. There was no difference in ABO blood group or Rh factor and tumor location. The highest A/O ratio was found in rectal cancer. Although there was no difference in stage distribution for each ABO blood group, there was a significant difference between the Rh+ and Rh- groups (P < 0.037). It is not clear, however, whether the prognosis is different between the two groups since there were more early tumors as well as incurable tumors in the Rh- group. All patients with synchronous cancer were Rh+. Further studies on blood group antigens are needed to elucidate the relationship between these antigens and colorectal cancer.

ABO Blood-Group System↗
PubMedDate not supplied

[Genetic aspects of the frequency of occurrence of suppurative highmoritis].

One hundred and fifty patients with chronic suppurative maxillary sinusitis (89 men and 61 women), aged 15 to 50 years, were examined. A potential correlation between the incidence of the disease and blood genetic markers (ABO-H blood group and Rh-factor) was investigated. No correlation was found between the incidence and ABO-H in that group of patients as a whole. The patients with documented staphylococcal nature of suppurative maxillary sinusitis belonged for the most part to the A (II) - Rh (D) + blood group.

ABO Blood-Group System↗
PubMed1994

Recombinant human insulin-like growth factor 1 (rh-IGF-1) stimulates erythropoiesis in adult, but not in newborn mice.

The in vivo effect of recombinant human insulin-like growth factor (rh-IGF-1) upon erythropoiesis was studied in inbred BALB/C mice. Unweaned, rapidly growing 20 days old mice and adult female mice received subcutaneous rh-IGF-1 or control injections every 6 h for 48 h. The mice were killed either 12 or 48 h after the last injection, i.e. a study time of 60 and 96 h, respectively. Bone marrow erythroid colony forming units (CFU-E), reticulocytes, haematocrit, serum immunoreactive erythropoietin (siEPO) and body and organ weight were measured. An additional group of young mice were given iron prior to the rh-IGF-1 injections to ensure sufficient available iron. No differences in overall body or organ weights were observed. In the young mice erythropoiesis as measured by bone marrow CFU-E, reticulocytes and haematocrit did not differ between rh-IGF-1 group and controls. When iron alone was given, reticulocytes (P < 0.05) and haematocrit (P < 0.0001) increased significantly, but no further stimulation was seen when rh-IGF-1 injections were given in addition to iron. The adult female mice responded with significantly increased erythropoiesis as judged by increased reticulocyte counts following rh-IGF-1 injections (P < 0.001). No significant effect upon CFU-E and haematocrit was detected. The reticulocyte response was more pronounced at 96 than at 60 h after the first rh-IGF-1 injection. SiEPO was significantly (P < 0.01) lower in the adult 96 h rh-IGF-1 group than in the appropriate control group. In conclusion parenteral iron significantly increased haematocrit in unweaned mice. Short time rh-IGF-1 treatment did not stimulate erythropoiesis in these rapidly growing mice, whether or not iron supplementation had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMedDate not supplied

Recombinant human granulocyte colony-stimulating factor reverts vascular dysfunction.

The aim of our study was to investigate the vascular effects of recombinant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure. Male anesthetized rats were subjected to the clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality rate (0% survival, 120 min following the release of clamps), a profound hypotension and vascular dysfunction consisting of a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings. Administration of recombinant human granulocyte colony-stimulating factor (20 micrograms/kg i.v. 5 min after the release of occlusion) increased survival rate (90% 4 h after the release of occlusion), blunted the profound hypotension and reverted the marked vascular dysfunction. Finally, rh G-CSF inhibited the activity of inducible nitric oxide synthase in peritoneal macrophages activated with endotoxin. Our data suggest that rh G-CSF may influence vascular function when low-flow states occur.

Acute Disease↗