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Correlation of anaphylactic bronchoconstriction with circulating reaginic antibody level and active cutaneous anaphylaxis in the rat.

The interrelationships of anaphylactic bronchoconstriction, active cutaneous anaphylaxis and circulating reaginic antibody level in rats sensitized with Nippostrongylus brasiliensis have been studied. The mean rise in bronchial reactivity during the 5-week sensitization period was correlated with the rise in circulating reaginic antibody level in groups of rats, although weak bronchial reactivity was observed before circulating reagin was demonstrable. In individual animals bronchial reactivity did not significantly correlate with circulating reaginic antibody level or cutaneous reactivity. Bronchial and cutaneous reactivity on challenge may be transferred to non-sensitized rats by passive sensitization with reaginic serum. It is concluded that the ability of a tissue to respond to antigen challenge is multifactorial and may not be reliably predicted from a knowledge of circulating reaginic antibody level or the response of another tissue in the same animal.

Anaphylaxis↗

Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating C56+ cells.

Intravenous (IV) immunoglobulin (Ig) has been previously shown to increase pregnancy rates after previously failed in vitro fertilization (IVF) embryo (ET) attempts in women who are efficient embryo producers (fertilize at least 50% of oocytes retrieved and generate at least 3 embryos/cycle). Women experiencing implantation failure have a higher frequency of elevated percentage of circulating CD56+ (natural killer) cells (>12%) than fertile women (3-12%). To evaluate the effects of IVIg on pregnancy rates in women with elevated percentage of circulating CD56+ cells, 32 women who had previously failed IVF/ET (>12 embryos transferred without pregnancy) were studied. Pregnancy and live birth rates with and without IVIg were compared in the same woman. All 32 women had previously failed to conceive after at least 12 ET, were efficient embryo producers and had persistently elevated plasma concentrations of CD56+ cells. Each woman received IVIg 500mg/kg prior to ET. If serum hCG concentrations were positive for pregnancy, IVIg was continued at 500mg/kg/mo until 28 weeks gestation. Pregnancy rates with and without IVIg were 56% and 9% (P<0.0001). The rate of live birth was 38% with IVIg and 0% without IVIg (P<0.0001). IVIg enhances pregnancy and live birth rates in women with elevated circulating CD56+ cells who have a history of implantation failure. Despite technologic advances leading to enhancement of fertilization rates after in vitro fertilization (IVF) (1, 2) implantation rates after embryo transfer (ET) have not increased significantly (3) over the last 20 years (4). Implantation rates after IVF/ET are influenced by the quality of the embryos and receptivity of the endometrium (3-9). Endometrial receptivity involves both hormonal (10-13) and immunologic (14-29) factors. Among the immunologic factors that play a crucial role in successful implantation are natural killer (NK) cells (14-18). NK cells present within the decidua that express CD56(but lack CD 16) have been associated with successful implantation (14-18). A deficiency of decidual CD56+ CD16- cells (18) and an increase in circulating CD56+ cells (25, 26) have been observed in women experiencing implantation failure. Women experiencing implantation failure after IVF and multiple ET have been successfully treated with intravenous (IV) immunoglobulin (Ig) (27). IVIg reduces activation of NK cells and NK killing activity both in vitro (29) and in vivo (30-31). This reduction in activation of NK cells is essential for normal implantation to occur (14). To further define the role of IVIg for treatment of implantation failure, pregnancy and live birth rates were compared before and after IVIg treatment in women undergoing IVF/ET who had elevated levels of circulating CD56+ cells.

Adult↗

Experimental ischaemia of the small intestine. Effect of antibiotic and antithrombotic drugs on the mucosal exchange circulation.

Factors of decisive importance for the fate of the intestine following circulatory occlusion incluse the bacterial flora of the intestine, intravascular thrombosis peripheral to the level of occlusion, and the capacity of the collateral circulation. Standardized ischaemia of the small intestine was produced in the rat by ligation of a given number of mesentric end arcades. The passive absorption of radioiodide from a defined, central loop within the ischaemic intestinal segment-as an expression of the exchange circulation of the intestinal mucosa-was determined 14 days after induction of the ischaemia. Different forms of treatment were studied. In Sprague-Dawley rats the effect of heparin, oxitetracycline (OCD) and a combination of these two drugs was examined both concerning the survival of the animals and with regard to the available exchange circulation in the mucosa of the ischaemic intestinal segment. The survival frequency was increased in all treatment groups. The exchange circulation in the ischaemic segment was improved significantly by ODC-treatment and by treatment with heparin and ODC combined. Treatment with heparin alone gave no improvement of the mucosal circulation.

Animals↗

The influence of sex hormones on circulating nitric oxide (NOx) levels in rhesus monkeys (Macaca Mulatta).

BACKGROUND: The effects of long-term estrogen (E2) replacement therapy (ERT) on circulating and bone marrow total plasma nitric oxide (NOx) levels were determined in rhesus monkeys. In addition changes in circulating NOx during the menstrual cycle were measured. MATERIAL/METHODS: We measured NOx levels in 20 ovariectomized animals and 27 cycling animals. In the first group monkeys were ovariectomized (OVX; n=10) and treated with estrogen implants for 21 months. The control group (n=10) was OVX and received vehicle implants only. After 21 months systemic NOx status was measured. In a second group of cycling animals NOx was measured during the follicular and luteal phases, and correlated with body composition parameters determined by dual energy X-ray absorptiometry (DXA) analysis. CONCLUSIONS: Replacement of estrogen in OVX monkeys resulted in reduced circulating but not bone marrow plasma NOx compared to OVX monkeys. Circulating NOx levels in these animals correlated negatively (r(2)= -0.35; P=0.03) with estradiol levels. In cycling monkeys luteal levels of NOx were found to be significantly higher than follicular levels and correlated negatively (r(2) = -0.4; P=0.036) with estradiol but not progesterone levels. Negative correlations between NOx levels and body weight, fat and lean mass were also found. RESULTS: Long-term ERT influences systemic NOx levels in a negative fashion without effects on bone marrow plasma NOx. Circulating NOx was higher during the luteal phase. In both ERT treated and cycling monkeys estradiol correlated negatively with NOx suggesting the existence of a negative feedback of NO on either NOS activity or expression.

Animals↗

Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure.

The association of excessive circulating androgens in blood and ovulatory failure in women is well documented in a variety of clinical conditions. The restoration of ovulatory function by wedge resection of the polycystic ovary, by the administration of glucocorticoids or removal of tumors of the adrenal or ovary--measures that also reduce the level of circulating androgens--is also well documented. In view of the many hypotheses of adrenal and ovarian abnormalities and disorders of the hypothalamic-pituitary axis in the human, resulting in hirsutism and ovulatory failure, a normal intact rat model was developed to study the effect of androgens on ovulation. The administration of a weak androgen, dehydroepiandrosterone (DHA), to immature rats resulted in a single precocious ovulation followed by ovulatory failure. The conversion of DHA to estrogens appeared to be the principle mechanism for the precocious ovulation. The steps appeared to be an elevation in blood estradiol, followed by the depletion of cytoplasmic estradiol receptors of the hypothalamus and pituitary and the gonadotropin surge leading to ovulation. These events appeared to be similar to those occuring in the adult cycling rat, in precocious puberty induced by the administration of pregnant mare serum gonadotropins and during the onset of natural puberty. The role of estrogens in inducing the precocious ovulation was further supported by the absence of precocious ovulation in animals in which the conversion of DHA to estrogens was blocked or by administering androgens that could not be converted to estrogens. In contrast, the subsequent ovulatory failure could not be explained entirely by the conversion of DHA to estrogens. There was a considerable time lag between the withdrawal of DHA treatment and the replenishment of pituitary and hypothalamic cytoplasmic estradiol receptors. Unlike those of the cycling animal, the receptors were not replenished when the levels of circulating estradiol in blood receded. The replenishment occurred only after the circulating levels of androstenedione, DNA and progesterone were reduced. Receptor replenishment in the hypothalamus and pituitary was followed by increases in the levels of circulating gonadotropins, particularly LH, with subsequent restoration of cyclic ovulatory function. The ovaries in the acyclic androgen-treated rat were responsive to gonadotropins. The pituitary responded to LH-RH administration, but the sensitivity was reduced. In the adult rat, ovulatory failure and the formation of polycystic ovaries took place with doses of DHA as low as 7.5 mg per kg of body weight. Attempts are being made to obtain further insights into the mechanism of androgen-induced ovulatory failure by studying the effect of androgens and progesterone on the steroid receptors and their function in the hypothalamus and the pituitary. Furthermore, a direct effect of DHA on the ovary, causing follicular atresia and cystic changes, is also being explored.

Animals↗

Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction.

The presence of circulating tumor cells in patients with localized or disseminated neuroblastoma may be a significant prognostic factor at diagnosis and may antedate the detection of relapse by other diagnostic studies. We report the development of a highly sensitive detection assay for circulating neuroblasts based on the reverse transcriptase-polymerase chain reaction (RT-PCR), using the neuroendocrine protein gene product 9.5 (PGP 9.5) as the tumor marker. Analysis of RT-PCR products by agarose gel electrophoresis demonstrated that neuroblastoma cell lines were uniformly positive, whereas peripheral blood mononuclear cells were negative. Alkaline Southern blotting with a PGP 9.5-specific probe revealed scant expression of PGP 9.5 in peripheral blood mononuclear cells, well below the limits of detection by electrophoresis alone. The system was able to detect a single neuroblastoma cell in 10(7) peripheral blood mononuclear cells. Eighteen patient samples were analyzed by PGP 9.5 RT-PCR and the results compared with immunocytology in 16. Ten of the 18 were negative by both studies. Eight of the 18 were positive by PGP 9.5 RT-PCR, 4 of which were also positive by immunocytology. PGP 9.5 RT-PCR was able to detect circulating neuroblasts in two patients with negative immunocytology, the first with progressive bone marrow disease and the second at high risk for relapse but no other evidence of disease. PGP 9.5 RT-PCR allows the detection of circulating neuroblastoma cells with a sensitivity greater than immunocytology. It will be useful in evaluating the clinical significance of circulating tumor cells with respect to prognosis and early detection of relapse, and in the screening of peripheral stem cell harvests prior to autologous infusion.

Base Sequence↗

[The effect of isoflurane or sevoflurane on circulating blood volume--a study under controlled ventilation].

Changes of circulating blood volume during isoflurane or sevoflurane anesthesia were investigated by the dual indicator dilution method in eighteen mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 6, isoflurane (I) group n = 6, and sevoflurane (S) group n = 6. The values of circulating blood volume (ml.kg-1) at 0, 0.5 and 1.0 MAC period were 90.1 +/- 18.7----87.5 +/- 17.2----94.1 +/- 23.6 in the I group and 91.6 +/- 12.5----96.5 +/- 15.0----94.1 +/- 8.5 in the S group, respectively. No significant changes were found in both groups concerning circulating blood volume, red cell volume, and plasma volume, but circulating blood volume and plasma volume tended to increase slightly in both groups at 0.5 and 1.0 MAC period compared with 0 MAC period. Mean arterial pressure decreased 68% of the initial value in the I group at the 1.0 and 78% stages in the S group. Cardiac index tended to increase from 2.6 +/- 0.4 l.min-1.m2 to 3.2 +/- 0.9 in the I group at the stage 1.0 but to decrease from 5.2 +/- 1.4 l.min-1.m2 to 4.1 +/- 0.9 in the S group. It was suggested that the increase of venous pressure resulted in the significant decrease of plasma volume. Increase of intrathoracic pressure during positive pressure ventilation might partially influence the blood volume change. Our data suggest that isoflurane and sevoflurane do not greatly affect the circulating blood volume under control ventilation.

Anesthesia, Inhalation↗

Clinical utility of the absolute number of circulating CD34-positive cells in patients with chronic myeloproliferative disorders.

BACKGROUND AND OBJECTIVES: Flow cytometry enumeration of peripheral blood CD34-positive cells provides reliable measurements of circulating hematopoietic progenitors in humans. Since the absolute number of circulating CD34-positive cells has been previously found to be elevated in myelofibrosis with myeloid metaplasia (MMM), we prospectively studied the clinical utility of this parameter in the work-up of patients with chronic myeloproliferative disorders. DESIGN AND METHODS: Of the 248 consecutive patients enrolled in this study, 106 had polycythemia vera (PV), 90 essential thrombocythemia (ET), and 52 myelofibrosis with myeloid metaplasia (MMM). The study population included both newly diagnosed and established cases, and of these latter some patients were on cytoreductive treatment while others were chemotherapy naive. Both cross-sectional and longitudinal investigations were carried out. Flow cytometry enumeration of CD34-positive cells was performed using a single-platform assay. RESULTS: Median numbers and ranges of circulating CD34-positive cells were 2.3x10(6)/L (0-5) in 20 control subjects, 2.2x10(6)/L (0-14) in those with PV, 2.4x10(6)/L (0-14) in those with ET, and 114x10(6)/L (6-2,520) in MMM patients. Analysis of variance demonstrated that values were markedly higher in MMM patients than in the remaining groups, and counts did not appear to fluctuate over short periods of follow-up. In both cross-sectional and longitudinal investigations on patients at clinical onset and/or out of cytoreductive treatment, a CD34-positive count of > or = 15x10(6)/L was always associated with MMM, clearly indicating a disease-related specificity. INTERPRETATION AND CONCLUSIONS: The absolute number of circulating CD34-positive cells is normal or anyhow lower than 15x10(6)/L in patients with uncomplicated PV or ET, whereas it is equal or above this cut-off in those with MMM, likely reflecting abnormal hematopoietic progenitor cell trafficking. Thus, enumeration of circulating CD34-positive cells may be useful in the work-up of patients with myeloproliferative disorders.

Adolescent↗

Expression of platelet endothelial cell adhesion molecule-1 between pancreatic microcirculation and peripheral circulation in rats with acute edematous pancreatitis.

OBJECTIVE: To study the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in rats with acute edematous pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: PECAM-1 expression on PMNs showed no significant difference between pancreatic microcirculation and peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated, but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1 expression had a significant difference between pancreatic microcirculation and peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1 expression on PMNs is in a converse way between pancreatic microcirculation and peripheral circulation in AEP.

Acute Disease↗

Circulating hematopoietic progenitor cells predict survival in patients with myelofibrosis with myeloid metaplasia.

BACKGROUND AND OBJECTIVES: The levels of circulating hematopoietic progenitor cells are often increased in myelofibrosis with myeloid metaplasia (MMM). The prognostic relevance of this phenomenon is largely unknown. DESIGN AND METHODS: We determined the number of circulating myeloid (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEMM) progenitors, in 110 patients with MMM at diagnosis using a semi-solid colony assay. Overall survival was investigated by plots of the Kaplan-Meier estimator; known risk factors and the number of circulating progenitor cells were tested by univariate and multiple Cox regression analysis. RESULTS: Univariate analysis showed that hemoglobin concentration (p=0.019), CFU-GM (p< 0.0001), BFU-E (p=0.002), and age (p=0.002) predicted survival. Numbers of circulating CFU-GM above the 75th percentile were associated with a significantly shorter survival than were CFU-GM levels at or below the 75th percentile (27 vs. 74 months, p=0.0007). Similarly, high numbers of BFU-E in peripheral blood (> 75th percentile) predicted a shorter survival (33 vs. 74 months; p=0.007). When myeloid and erythroid progenitor cells were calculated separately in the multiple Cox regression analysis, both CFU-GM (hazard ratio 2.8, 95% CI, 1.35 to 5.93) and BFU-E (hazard ratio 2.57, 95% CI, 1.26 to 5.21) numbers above the 75th percentile were independent adverse prognostic factors in our patients. INTERPRETATION AND CONCLUSIONS: High levels of circulating myeloid and erythroid progenitor cells are novel risks factors in patients with MMM. The assessment of hematopoietic progenitor cells may be useful to determine risk-adjusted treatment strategies.

Adult↗

[Life achievements of Dr. Dusan Kentera (1925-1999). Aspects of pulmonary circulation].

Dusan Kentera was born on April 2nd 1925 in Stip. He finished high school in Belgrade in 1944, graduated from Medical school, University of Belgrade in 1951, and completed his internal medicine residency in 1957. In 1960 he fulfilled the requirements for the teaching position at the University with a thesis "The use of dilution methods in the study of circulation" and defended his PhD thesis "Hemodynamic characteristics of pulmonary hypertension with increased precapillary resistance" in 1964 at the School of Medicine, University of Belgrade. Dusan Kentera was awarded Swedish government's scholarship in 1958 and spent a year in the laboratory of Gustav Nylin in Stockholm. As a fellow of the National Institutes of Health, he spent 15 months at the Institute of Physiology at The Medical College of Georgia in Augusta, USA, in the Laboratory of William F. Hamilton in 1962 and 1963. As a "visiting scientist" he spent three months in Memorial Research Center, University of Tennessee, in Knoxville, USA, in 1972. In 1980 and again in 1988 Dusan Kentera gave a series of lectures at leading medical research institutions in USA, including Medical School, University of Colorado in Denver, Tulane University Medical School in New Orleans, University of Tennessee Medical School in Memphis, and Texas Research and Rehabilitation Institute in Houston. He spent his career in research at the Institute for Medical Research in Belgrade, where he was appointed Research Fellow in 1952 and became Professor of Research in 1976. Simultaneously, he held teaching position at the Institute of Physiology, School of Dentistry, University of Belgrade, where he was appointed first Instructor in 1952 and full Professor in 1977. In 1964, Dusan Kentera founded the Laboratory for Hemodynamics at the Institute for Medical Research, which he headed until retirement in 1991. He was Assistant Director of the Institute for Medical Research from 1974 until 1978 and Director from 1978 until 1991. He was very much involved in postgraduate teaching at the Medical School, University of Belgrade, where he lectured at the courses in Pulmonary Diseases and Cardiology until death. Numerous Master and PhD theses were completed under his mentorship and in his Laboratory. Many of his students hold at present leading positions in academic institutions worldwide. As a researcher, Dusan Kentera has an outstanding record. He published 120 papers in peer-reviewed journals and authored chapters in several books. Main research interest of Dusan Kentera was related to cardiovascular pathophysiology, particularly in the fields of regulation of pulmonary circulation and pathogenesis of hypoxic pulmonary hypertension, control mechanisms in systemic circulation and pathogenesis of arterial hypertension, contractility of skeletal muscles and myocardium, and control mechanisms in regional circulation. Most impressive, by significance and extent, is his work on the regulation of pulmonary circulation and particularly on the pathogenesis of hypoxic pulmonary hypertension. Most of the research on hypoxic pulmonary hypertension was done on experimental model that he established. As opposed to all other models, which employed hypobaric hypoxia with consequent hypocapnia, in his model experimental animals were exposed to normobaric hypoxia and controlled level of carbon dioxide, thus most closely simulating hypoxic pulmonary hypertension in humans. Using this model, he examined the role of numerous factors in the pathogenesis of acute and chronic hypoxic pulmonary hypertension. His pioneering work in this field is well incorporated into today's understanding of the pathophysiologic mechanisms underlying hypoxic pulmonary hypertension as well as in therapeutic approaches to this disorder Dusan Kentera was always recognized as an outstanding figure in scientific community, yet awards and formal acknowledgments somehow by-passed him. He did share though the October Award of the City of Belgrade for research with his long time friend Dr. Vladislav Varagić in 1976. Dusan Kentera died on his birthday, April 2nd 1999. As an inspired teacher, outstanding scientist, authoritative leader and, above all, as wonderful human being, he set high standards for coming generations. It is on his disciples to carry on.

History, 20th Century↗

[Change of circulating TNF-alpha in patients with advanced periodontitis before and after periodontal initial therapy].

OBJECTIVE: To investigate the effect of periodontal initial therapy on circulating tumor necrosis factor-alpha (TNF-alpha) in patients with periodontitis. METHODS: Patients with advanced periodontitis were selected. Sulcus bleeding index (SBI), probing depth (PD), and circulating TNF-alpha concentration were assessed respectively before and 4-6 weeks after periodontal initial therapy. RESULTS: The level of circulating TNF-alpha in patients with periodontitis was significantly higher than that in healthy control subjects (P < 0.01). After periodontal initial therapy, SBI, PD and circulating TNF-alpha concentration were reduced significantly (P < 0.01) in patients with periodontitis. CONCLUSION: Periodontitis may have profound effects on systemic health through the elevation of circulating TNF-alpha. Prevention and treatment of periodontitis should be important in maintaining systemic health.

Adult↗

Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation.

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.

6-Ketoprostaglandin F1 alpha↗

The relationship between circulating carcinoembryonic antigen (CEA) levels and parameters of primary tumor and metastases in breast cancer patients.

AIM: The Carcinoembryonic antigen (CEA) is used as a tumor marker for breast cancer (BC). In order to better define clinical usefulness of CEA in breast cancer patients (BCP) we determined its baseline pre-treatment levels and correlated them with main parameters of primary tumor and metastases. PATIENTS AND METHODS: The main experimental group consisted of 47 female patients with histologically confirmed diagnosis of BC. The obtained results have been compared with those of two control groups: clinically healthy women, and patients with other types and locations of cancer. In both cancer groups the parameters of primary tumor (size, grade) and metastases (time interval to metastases, location, size) have been determined. Circulating levels of CEA were measured by the means of immunoradiometric assay. Results were processed by means of t-test, two way analysis of variance in F-test, and logistic general linear model with calculations of Pearson's correlation coefficient. RESULTS: Baseline levels of CEA in BCP were significantly higher than in healthy women (p < 0.0001), and in patients with other types and locations of cancer (p < 0.007). There also was significant difference (p < 0.001) between serum CEA in other cancer patients and healthy women. Baseline CEA levels were in significant positive correlation with the size of primary tumor both in all BCP (p < 0.03) and in hyperCEA BCP (p < 0.002), while in other cancer patients such a correlation did not exist. There was no correlation between CEA and degree of differentiation of primary tumor either in BCP or in other cancer patients. The average circulating levels of CEA in metastatic BCP were significantly higher (p < 0.03) in comparison to non-metastatic patients, while in other cancer patients such a difference did not show up. There was significant correlation (p < 0.0001) between circulating CEA and the size of metastases in all BCP and in subgroup of hyperCEA BCP, while in other cancer patients it was not a case. There was no correlation between serum CEA and other two metastatic parameters either in BCP or in other cancer patients. CONCLUSIONS: CEA does not have high tumor specificity for BC since its baseline levels may be elevated in other types of cancer. Circulating levels of CEA in BCP are directly dependable on the size of both primary and metastatic tumor. CEA is a tumor antigen of less differentiated cancer cells. Circulating CEA is a good prognostic marker for patients with metastatic BC.

Adolescent↗

Circulating vaccine-derived polioviruses: current state of knowledge.

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.

Child↗

Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes.

The proteins associated with liposomes in the circulation of mice were analyzed in order to determine whether bound proteins significantly influence the fate of liposomes in vivo. Liposomes were administered intravenously via the dorsal tail vein of CD1 mice and were isolated from blood after 2 min in the absence of coagulation inhibitors using a rapid "spin column" procedure. Various negatively charged liposomes exhibiting markedly different clearance properties were studied; notably, these included liposomes containing 10 mol % ganglioside GM1 which has been previously shown to effectively limit liposomal uptake by the fixed macrophages of the reticuloendothelial system. The protein binding ability (PB; g of protein/mol of lipid) of the liposomes was quantitated and related to the circulation half-life (tau 1/2) of the liposomes. Liposomes having similar membrane surface charge imparted by different anionic phospholipids were found to exhibit markedly different protein binding potentials. Furthermore, PB values determined from the in vivo experiments were found to be inversely related to circulation half-lives. PB values in excess of 50 g of protein/mol of lipid were observed for rapidly cleared liposomes such as those containing cardiolipin or phosphatidic acid (tau 1/2 less than 2 min). PB values for ganglioside GM1-containing liposomes (tau 1/2 greater than 2 h) were significantly less (PB less than 15 g of total protein/mol of total lipid). PB values were also determined for liposomes recovered from in vitro incubations with isolated human serum; relative PB values obtained from these in vitro experiments were in agreement with relative PB values measured from in vivo experiments. PB values, therefore, could be a useful parameter for predicting the clearance behavior of liposomes in the circulation. Liposomes exhibiting increased PB values in vivo were shown by immunoblot analysis to bind more immune opsonins, leading to a higher probability of phagocytic uptake. Finally, based on results obtained using the in vitro system, it is suggested that the mechanism by which ganglioside GM1 prolongs the murine circulation half-life of liposomes is by reducing the total amount of blood protein bound to the liposomes in a relatively nonspecific manner.

Animals↗

Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review.

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.

Biomarkers, Tumor↗

[Presence of circulating cytomegalic cells in HIV negative immunosuppressed individuals following cytomegalovirus infection].

OBJECTIVE: Immunofluorenscence methods to detect pp65 antigenemia were implemented for identifying the circulating virus-infected cells in individuals known to have cytomegalovirus infection and disease symptoms. MATERIAL AND METHODS: Between December-2002 and July-2003, 110 peripheral blood samples were obtained from 46 immunosuppressed patients. pp65 antigenemia and the presence of circulating cells were determined by indirect immunofluorescence using a commercial kit to detect CMV pp65 antigen in peripheral blood leukocytes. Antigenemia was positive when one or more cells was observed with multilobulated, homogenous fluorescent stain in the nucleus. The presence of infected circulating cells (peripheral blood mononuclear cells) was determined when an extended pattern of fluorescent stain was observed throughout the cytoplasm in cells of 35 to 50 microm. RESULTS: Eight antigenemias from 7 patients (15%) were positive. Of these, 4 (57%) were also positive for circulating infected cells and consisted of 3 kidney transplant recipients and 1 liver transplant recipient. The number of positive cells in antigenemia was greater in kidney-transplant recipients than in the rest of immunosupressed patients (457 vs. 1.96, p < 0.005). No association was seen between the presence of infected circulating cells, morbidity, mortality or the development of GVHD (p < 0.001). CONCLUSION: No correlation was observed between the presence of infected cells, antigenemia and mortality. To substantiate the lack of correlation amongst these factors, prospective studies with larger sample sizes are necessary. These studies will aid in better defining the clinical application in immunosupressed patients.

Antigens, Viral↗