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PubMed2001

Hematocrit correlates well with circulating red blood cell volume in very low birth weight infants.

Although circulating red blood cell (RBC) volume is a better measure of total body oxygen delivering capacity than hematocrit (HCT), circulating RBC volume is more difficult to measure. Thus, the HCT is often used in RBC transfusion decisions. However, several previous studies of low birth weight infants have reported that the correlation between HCT and circulating RBC volume is poor. Using a robust nonradioactive method based on in vivo dilution of biotinylated RBC enumerated by flow cytometry, the present study reexamined the correlation between HCT and circulating RBC volume in very low birth weight infants. Venous and capillary HCT levels were compared with circulating RBC volume measured using the biotin method. Twenty-six stable very low birth weight infants with birth weights less than 1300 g were studied on 43 occasions between 7 and 79 d of life. Venous HCT values correlated highly with circulating RBC volume (r = 0.907; p < 0.0001). However, the mean 95% confidence limits for prediction of circulating RBC volume from venous HCT (the average error of prediction) was +/-13.4 mL/kg. The correlation between HCT and circulating RBC volume is strong in older stable very low birth weight infants. However, clinically important uncertainty exists in estimating circulating RBC volume and the associated RBC transfusion needs of an individual infant based on venous HCT. Because direct measurement of circulating RBC volume is not yet practical, the HCT (or the blood Hb concentration) remains the best available indirect indicator.

Erythrocyte Transfusion↗
PubMed2002

Circulating concentrations of "free" leptin in relation to fat mass and appetite in gastrointestinal cancer patients.

Recent studies have suggested that circulating concentrations of leptin might play a role in cancer cachexia. In the first part of the study, we compared circulating concentrations of free and total leptin, percent fat mass, and the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), together with appetite score, in age- and gender-matched healthy controls (n = 11) and advanced gastrointestinal cancer patients (n = 26). In the second part of the study, the same measurements were repeated before and after megestrol acetate treatment of weight-losing gastrointestinal cancer patients (n = 10). Body mass index and percent fat mass were significantly lower (P < 0.05) and IL-6 and CRP were significantly higher (P < 0.05) in cancer patients than in controls. There was no difference in the percentage of leptin bound in the circulation between controls and cancer patients. Circulating "free" leptin concentrations correlated with percent fat mass in controls (r = 0.745, P = 0.008) and cancer patients (r = 0.600, P = 0.001). In cancer patients, circulating leptin concentrations, either free or total, were not correlated with IL-6 or CRP concentrations. When adjusted for fat mass, the circulating concentrations of free and total leptin were significantly lower in the cancer patients (P < 0.01). Megestrol acetate treatment significantly increased circulating free and total leptin concentrations in the cancer patients (P < 0.05). There was a significant positive correlation between the change in circulating concentrations of free and total leptin and the change in percent fat mass (r = 0.685, P < 0.05 and r = 0.661, P < 0.05, respectively). The results of the present study indicate that the proportions of free and bound leptin in the circulation do not differ between normal subjects and patients with gastrointestinal cancer and in both groups are related to fat mass. Furthermore, the increase in circulating leptin concentrations after megestrol acetate treatment is not associated with any alteration in leptin binding.

Aged↗
PubMed1997

Nutritional regulation of circulating insulin-like growth factors (IGFs) and their binding proteins in the ovine fetus.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important for fetal and postnatal development, but the regulation of circulating IGFs and IGFBPs has not been as thoroughly investigated in the maternal/fetal unit as in the adult animal where nutrition status plays a regulatory role. We used the chronically-catheterized, late-gestation ovine model and compared circulating IGFs and IGFBPs levels, and hepatic IGF-I mRNA levels. Following a five-day maternal fast, both IGF-I and IGF-II levels were decreased in the maternal and fetal circulation (P < 0.05), accompanied by a decrease in fetal hepatic IGF-I mRNA levels, but the IGFBP2 level was increased and the IGFBP3 level was decreased in maternal circulation, whereas the IGFBP1 level was increased in fetal circulation. In both fed and fasting states, the infusion of glucose (150% of baseline) did not alter IGFs or IGFBPs in either maternal or fetal circulation. To understand the regulation of the endogenous IGF system, rhIGF-I was infused (6.7 nmol/kg fetus/h) into the fetal circulation. While maternal IGFs or IGFBPs remained unchanged, IGF-I infusion into fetal circulation resulted in an increase in IGF-I, a decrease in IGF-II, and an overall increase in the IGFBPs (P < 0.05). Taken together, circulating IGFs and IGFBPs in the ovine fetus are more sensitive to prolonged nutrient deficit than to a brief glucose increase. The nutrition status therefore regulates the IGF system in maternal and fetal circulation which, in turn, may regulate the nutrient utilization for fetal growth.

Animals↗
PubMed2002

[Study on pharmaceutical characterization and pharmacokinetics of daunorubicin long-circulating liposomes in rat].

AIM: To study the pharmaceutical characterization and pharmacokinetics of long-circulating liposomes containing daunorubicin. METHODS: The morphology of daunorubicin long-circulating liposome was surveyed under the transmission electron microscope. The size of daunorubicin long-circulating liposomes was determined by laser scatter method. The entrapment efficiency and accelerative experiment stability of the daunorubicin long-circulating liposomes were examined. Visible spectrophotometry and the HPLC method were established for determination of the daunorubicin in the long-circulating liposomes. The percent release of daunorubicin from long-circulating liposomes in HBS (pH 7.5) and rat serum at 37 degrees C were examined. The pharmacokinetics in rats were studied. RESULTS: The high entrapment efficiency (> 85%) and stabilized long-circulating liposomes could be achieved. The drug was slowly released from the daunorubicin long-circulating liposomes. The drug released from liposomes was less than 10% in 24 h. The T1/2 alpha and AUC of long-circulating liposome were higher than those in injections. CONCLUSION: The long-circulating liposomes prepared by us have high encapsulation efficiency and the pharmaceutical characterization showed good stability, they can be used for clinical purpose.

Animals↗
PubMed1996

Immune-mediated subepithelial blistering diseases of the mucous membranes. Improving the detection of circulating autoantibodies by the use of concentrated serum samples.

BACKGROUND AND DESIGN: Comparison of detection of circulating autoantibodies before and after concentration of serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes. We determine whether the use of concentrated serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes improves diagnostic sensitivity for circulating antibodies. We studied 13 patients from a university-based referral practice who had no skin lesions and a scarring subepithelial blistering disease of the mucous membranes. Three of these patients had detectable circulating autoantibodies and 10 had negative indirect immunofluorescence study results using standard techniques. The main outcome measures after concentration of serum samples were detection of circulating autoantibodies on salt-split skin by indirect immunofluorescence, immunoblotting, and immunoprecipitation. RESULTS: Of the 10 patients in whom circulating autoantibodies had not been detectable with standard techniques, circulating IgG antibodies were detected in 5 (50%) and circulating IgA antibodies in 3 (30%). Of the 3 patients in whom circulating autoantibodies had been detectable with standard techniques, 1 (33%) had circulating IgA antibodies that immunoblotted the 97-kd linear IgA bullous disease antigen only when concentrated serum samples were used. CONCLUSIONS: The use of concentrated serum samples can improve our ability to detect the presence and antigenic specificity of circulating autoantibodies in patients with suspected but unclassifiable immune-mediated subepithelial blistering diseases of the mucous membranes.

Autoantibodies↗
PubMed2003

Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates.

BACKGROUND: We developed an extracorporeal liver perfusion (ECLP) system as a liver-assist device. In this study, we evaluated the safety of the ECLP using human decay accelerating factor (hDAF) transgenic porcine livers in healthy baboons. METHODS: Livers were isolated from five hDAF transgenic pigs and five nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and healthy baboons were performed without immunosuppressive agents. Cross-circulation was discontinued in any of the following circumstances: elevated hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24-hr well-conditioned cross-circulation. RESULTS: The cross-circulations with nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three cross-circulations with hDAF transgenic porcine livers were performed for 24 hr; the other two cross-circulations were discontinued at 13 and 17 hr because of massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1 hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver was less than that in the nontransgenic liver, although immunoglobulin-M deposition was comparable. The porcine livers showed no apparent interlobular bleeding or lobular necrosis. All porcine livers maintained bile production during the cross-circulation. No baboons showed any serious complications after the cross-circulation. CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.

Animals↗
PubMedDate not supplied

[Stress and blood circulation in man].

This paper presents the results of studying stress effects on the heart, systemic circulation and cerebral circulation by various methods (ECG, Doppler technique, isotopes, etc). Patterns of circulation changes in response to mental stresses have been identified and variations in circulation regulation as a function of stress enhancement have been revealed. Cerebral circulation changes produced by heavy mental work under stressful conditions are described (increase of blood flow velocity in carotid arteries and of tone of cerebral arteries of large and medium caliber, change in reactivity of anastomoses between branches of the internal and external carotid arteries, patterns of increase and decrease of blood flow in the gray matter of the brain cortex). During prolonged bed rest the type of stressor changes in blood circulation becomes modified and susceptibility to hypertensive states developed. In the course of stressor reactions circulation parameters vary substantially. In this situation changes in systemic circulation are closely related to emotional responses and those in cerebral circulation--to adaptive processes supporting mental activities.

Blood Circulation↗
PubMed1993

The transition from fetal to neonatal circulation: normal responses and implications for infants with heart disease.

The primary function of the circulatory system of both the fetus and newborn is to deliver oxygen to metabolizing organs and return deoxygenated blood to the gas exchange organ to replenish the oxygen and eliminate the waste product CO2. In the fetus, the gas exchange organ is the placenta, and its vascular connections are in a parallel arrangement with the other systemic organs, remote from the pulmonary circulation. In order to supply deoxygenated blood to the placenta and return oxygenated blood to the systemic organs, a series of extracardiac shunts (ductus venosus, ductus arteriosus) and an intracardiac communication (foramen ovale) are necessary. With birth, the function of gas exchange is transferred from the placenta to the lungs, and therefore from the systemic circulation to the pulmonary circulation. The venous and arterial circulations are separated, and not only are the fetal shunts unnecessary, but their persistence may lead to circulatory compromise. The transition from the fetal to the neonatal circulation thus includes elimination of the placental circulation, lung expansion, and increase in lung blood flow so that the entire cardiac output can be accommodated, and closure of the foramen ovale, ductus arteriosus, and ductus venosus. For most congenital structural heart disease, the fetal shunt pathways allow redistribution of ventricular blood flows so that systemic blood flow is adequate and fetal growth and development are usually normal. Uncomplicated VSDs do not alter the circulation significantly in either the fetus or immediate newborn period, with the important exception of premature infants. With severe left heart obstruction, the burden of systemic and pulmonary blood flow is transferred to the fetal right ventricle, with reversal of blood flow at the foramen ovale, and systemic blood flow almost entirely transmitted via the ductus arteriosus. This "ductal-dependent" systemic circulation is poorly tolerated in the newborn, because normal closure of the ductus arteriosus progressively decreases systemic blood flow and progresses to circulatory failure and shock. Severe right heart obstruction is also well tolerated in the fetus, because the combined fetal cardiac output can be transferred to the aorta, with the ductus arteriosus supplying predominantly lung blood flow. After birth, such "ductal-dependent" pulmonary blood flow can lead to critically low levels of pulmonary blood flow and severe cyanosis with closure of the ductus arteriosus. An understanding of fetal hemodynamics and the acute and chronic changes that occur with transition to the newborn circulation are important for the care of normal newborns and are crucial to the recognition, diagnosis, and management of the newborn with significant congenital heart disease.

Animals↗
PubMed1985

Collateral circulation in coronary artery disease.

The coronary arteriograms and left ventriculograms of 202 consecutive patients were reviewed. All had at least 75% diameter reduction of 1 or more major coronary arteries. In 127 patients (63%), at least 1 major branch was totally occluded. Collateral circulation was seen in 125 of these 127 patients (190 of 192 totally occluded arteries). Of the 75 patients without total occlusion, only 2 with 99% (or near-total) occlusion had demonstrable collateral circulation (2 of 208 arteries). In no patient with 75 to 98% diameter narrowing was collateral circulation demonstrated (0 of 164 arteries). An analysis was made of the relation between left ventricular (LV) segmental wall motion and the quality of collateral circulation in 190 totally occluded arteries among 125 patients. Of 126 arteries with good collateral circulation, LV contraction was normal in 21%, hypokinetic in 48% and akinetic/dyskinetic in 29%. Of 64 arteries with poor collateral circulation, LV contraction was normal in 23%, hypokinetic in 55% and akinetic/dyskinetic in 20%. There was no statistically significant difference between the effect of good or poor collateral circulation on LV function. These data indicate that collateral circulation cannot be seen angiographically unless there is total or near-total occlusion, and that the presence of collateral circulation does not correlate with LV wall motion abnormalities, i.e., akinetic area, despite good collateral flow or normal wall motion despite absent or poor collateral flow.

Collateral Circulation↗
PubMed1997

Effects of heparin-coating of cardiopulmonary bypass circuits on leukocytes during simulated extracorporeal circulation.

Heparin-coated circuits used during extracorporeal circulation reduce many postoperative complications occurring after heart surgery. Such complications are partly related to leukocyte activation with subsequent release of active substances, e.g. oxygen free radicals, myeloperoxidase and lactoferrin. This experiment was performed to elucidate a possible influence of heparin-coating on leukocytes. A 2-h-long simulated extracorporeal circulation was performed on two groups of five extracorporeal circulation circuits, primed with heparinized, fresh whole human blood and Ringer's solution. Heparin-coated circuits (HC group) were compared with uncoated circuits (NC group). Oxygen free radical production was estimated by determination of malonyldialdehyde in plasma and erythrocyte suspension. Granulocyte activation was measured in terms of myeloperoxidase and lactoferrin release. Time-related changes in leukocyte subset counts were analysed. Heparin-coating diminished myeloperoxidase and lactoferrin release. There were significant inter-group differences after 90 and 120 min of extracorporeal circulation for myeloperoxidase (101 (12) microg/l and 107(12) microg/l in the HC group versus 154(20) microg/l and 174(23) microg/l in the NC group), and after 120 min of extracorporeal circulation for lactoferrin (78(5) microg/l in the HC group versus 212(49) microg/l in the NC group). No significant changes of MDA concentration were observed in plasma or erythrocytes; however, a tendency towards lower MDA levels was seen after 90 and 120 min of extracorporeal circulation in the NC group. Neutrophil, monocyte and eosinophil numbers decreased significantly in the NC group but were unchanged in the HC group, as were lymphocyte counts. Heparin-coated extracorporeal circulation circuits significantly reduce granulocyte activation and better preserve the number of circulating neutrophils, eosinophils and monocytes, but do not change oxygen free radical production during simulated extracorporeal circulation.

Anticoagulants↗
PubMed1999

Role of the splanchnic circulation in acid-base balance during cardiopulmonary bypass.

OBJECTIVE: The role of the splanchnic circulation in the development of the metabolic acidosis of cardiopulmonary bypass (CPB) is not fully understood. New quantitative methods of acid-base balance now offer the ability to define this phenomenon more accurately. Accordingly, we studied acid-base changes across the splanchnic circulation during CPB and defined and quantified the factors that contributed to acid-base balance. DESIGN: Prospective cohort study. SETTING: Tertiary institution. PATIENTS: Ten patients undergoing CPB for coronary artery bypass surgery. INTERVENTIONS: Sampling of arterial and hepatic venous blood at four time intervals: postinduction, on CPB during cooling and rewarming, and at skin closure. MEASUREMENTS: Measurement of serum Na+, K+, Mg++, Ca++, Cl-, HCO3-, and phosphate concentrations, arterial and hepatic venous blood gases and serum albumin, and lactate and pyruvate concentrations at each collection point. Analysis of findings according to quantitative physicochemical principles. MAIN RESULTS: All patients developed a mild metabolic acidosis with a decrease in median serum bicarbonate concentration from 24.97 mEq/L after induction to 22.29 mEq/L at cooling and 22.23 mEq/L at rewarming (p < .05). Before CPB, the pH decreased by 0.0275 (p < .05) across the splanchnic circulation, representing an increase of 2.26 nmol/L of hydrogen ions. Nevertheless, the splanchnic circulation induced a metabolic alkalosis, with a median transsplanchnic increase in the base excess of 1.50 mEq/L (p < .05). This change was largely due to a decrease in serum chloride and lactate concentration across the splanchnic circulation (p < .05). The acidifying effect of the splanchnic circulation was therefore the result of cell respiration with a median increase in carbon dioxide tension of 5.75 mm Hg (p < .05), causing the strong ion difference effective to increase by 1.94 mEq/L (p < .05). There were no other anions or acids added to the circulation by splanchnic organs (no change in strong ion gap). During and after CPB the splanchnic metabolic alkalinizing effect continued and the respiratory acidifying effect was reduced. This caused the splanchnic circulation to be pH neutral at these times. CONCLUSIONS: Using quantitative biophysical methods it can be demonstrated that the splanchnic circulation does not contribute to the metabolic acidosis of CPB, and that it continues to have a metabolic alkalinizing effect involving significant lactate extraction. However, its respiratory acidifying effect continues, although at a reduced rate.

Acid-Base Equilibrium↗
PubMed2004

Circulating CD34-positive cells provide an index of cerebrovascular function.

BACKGROUND: Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34- and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction. METHODS AND RESULTS: The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34- and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34- and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion. CONCLUSIONS: These results suggest a possible contribution of circulating CD34- and CD133-positive cells in maintenance of the cerebral circulation in settings of ischemic stress. Our data demonstrate the utility of a simple and precise method to quantify circulating CD34-positive cells, the latter providing a marker of cerebrovascular function.

AC133 Antigen↗
PubMed1990

The influence of extracorporeal circulation on erythrocytes and flow properties of blood.

The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting. Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation. Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours. Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible. Red cell membrane lipids were not affected. Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation. This suggests an increased proteolytic activity of the plasma after extracorporeal circulation. Red cell deformability was not altered. Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution. Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C. We conclude that the red cell is affected by extracorporeal circulation. The flow properties of blood, however, are not impaired, but are improved by hemodilution.

Aged↗
PubMed1976

Mean retinal circulation time as determined by fluorescein angiography in normal, prediabetic, and chemical-diabetic subjects.

A preliminary survey has been completed using manual densitometric technics to determine the mean retinal circulation times in groups of normal controls, offspring to two diabetic parents with normal glucose tolerance (prediabetics), and offspring of two diabetic parents with abnormal glucose tolerance (chemical diabetics). Comparisons of the mean retinal circulation time showed differences between the left eye and right eye in prediabetic and chemical diabetic groups and a sex difference in both normals and prediabetics. In addition, both age and per cent ideal body weight were inversely related to the mean retinal circulation time. The levels of fasting serum cholesterol, triglyceride, and growth hormone, in many instances, also appeared to be inversely related to the mean retinal circulation time. Similarly, the degree of glucose tolerance (determined by the area under the glucose curve above baseline) was significantly inversely related to the mean retinal circulation time. The mean retinal circulation time adjusted for per cent ideal weight was analyzed separately for both right eye and left eye, and a significantly shorter mean retinal circulation time was noted, particularly in males, for prediabetics than for normal controls and for chemical diabetics than for both prediabetics and normals. Analysis of the mean retinal circulation time adjusted for age showed similar differences. It is postulated that the genetic prediabetic state with or without glucose intolerance might be associated with significant alterations of mean retinal circulation time independent of age and per cent ideal weight. It is also suggested that a number of potentially meaningful interrelationships between the degree of glucose intolerance and/or hyperlipidemia might exist and should be further quantified.

Adult↗
PubMed1997

[Detection of circulating neoplastic cells by reverse transcriptase and polymerase chain reaction in melanoma].

BACKGROUND: Circulating melanocytes can be detected in peripheral blood of patients with malignant melanoma by means of tyrosinase messenger RNA amplification. In this study we especially examined peripheral blood from patients with stage II melanoma before and after lymph node dissection for the detection of these circulating melanoma cells. Indeed the presence of regional nodal metastasis is one of the most important prognostic factors in patients with cutaneous melanoma. PATIENTS AND METHODS: Blood samples were collected from 20 normal patients, 42 patients with stage I melanoma and 23 patients with stage III melanoma. Twenty patients with stage II melanoma were tested 3 days before lymph node dissection and 2 à 8 weeks after. To identify circulating melanocytes, we used coupled reverse-transcription and polymerase chain reaction to target tyrosinase messenger RNA. RESULTS: None of the 20 patients with stage II melanoma had detectable circulating melanocytes before lymph node dissection. By contrast, 7 of them became transiently PCR positive in the 8 weeks following surgery. We observed no evidence of correlation between the presence of circulating melanocytes after lymph node dissection and the risk of relapse within 6 months after surgery or the presence of capsule breaking or the number of involved lymph nodes. Sixty-nine percent of stage III patients and none of stage I patients were found to have circulating melanocytes. DISCUSSION: Our study suggests that melanoma cells could circulate transiently after lymph node dissection. Confrontation of our results with literature data, despite important discrepancies related in part to sensibility technique, shows that the presence of circulating melanoma cells is correlated to the clinical stage. Prognostic value of these circulating cells need to be further assessed by prospective studies with large number of patients and long follow-up.

Gene Expression Regulation, Enzymologic↗
PubMed2002

Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis.

Tumor cells are characterized by specific genetic alterations. When such genetic alterations are identified in body fluid including plasma, regardless of the presence of detectable tumor cells, it shows the existence of free-circulating tumor-associated DNA. The objective of our study was to assess the prognostic value of free-circulating tumor-associated DNA in colorectal cancer patients' plasma. The first step of our work was to find common genetic alterations in tumors that would subsequently be used for plasma DNA screening. We focused on KRAS2 mutations in codons 12 and 13 by the mutant allele-specific amplification (MASA) method and p16 hypermethylation by the methylation-specific polymerase chain reaction (MSP) method. Patients with a tumor presenting either alteration were selected for plasma screening; 58 tumors were analyzed for KRAS2 mutations and tested for p16 gene promoter methylation. Survival and recurrence rates were assessed in patients with and without free-circulating tumor-associated DNA alterations in plasma. Of the 58 tumors analyzed, 39 (67%) demonstrated either one or both of the studied genetic alterations. Twenty-two (38%) were mutated at KRAS2, and an identical alteration was detected in 10 (45%) of the 22 corresponding plasma samples. Thirty-one (53%) had p16 gene promoter hypermethylation that could also be detected in the plasma in 21 cases (68%). Among the 39 patients who had one or the other alteration in tumor DNA, 37 had at least one reliable plasma test. In 26 (70%) of the 37 patients, free-circulating tumor-associated DNA was detected in plasma. The 2-year overall survival rate was 48% in the group where free-circulating tumor-associated DNA was detected in plasma and 100% in the one where free-circulating tumor-associated DNA was not detected in plasma (p < 0.03). Among these 37 patients, 25 patients had a stage I, II or III disease. In this subgroup of patients, the 2-year recurrence-free survival rate for the 17 patients with free-circulating tumor-associated DNA detected in plasma was 66%, compared to 100% for the 8 patients without free-circulating tumor-associated DNA detected in plasma (p = 0.044). The presence of free-circulating tumor-associated DNA in plasma seems to be a relevant prognostic marker for patients with colorectal cancer and may be used to identify patients with a high risk of recurrence.

Adult↗
PubMed2005

Diagnostic developments involving cell-free (circulating) nucleic acids.

BACKGROUND: The detection of circulating nucleic acids has long been explored for the non-invasive diagnosis of a variety of clinical conditions. In earlier studies, detection of circulating DNA has been investigated for the detection of various forms of cancer. Metastasis and recurrence in certain cancer types have been associated with the presence of high levels of tumor-derived DNA in the circulation. In the case of pregnancies, detection of fetal DNA in maternal plasma is a useful tool for detecting and monitoring certain fetal diseases and pregnancy-associated complications. Similarly, levels of circulating DNA have been reported to be elevated in acute medical emergencies, including trauma and stroke, and have been explored as indicators of clinical severity. Apart from circulating DNA, much attention and effort have been put into the study of circulating RNA over the last few years. This area started from the detection of tumor-derived RNA in the plasma of cancer patients. Soon after that, detection of circulating fetal RNA in maternal plasma was described. Plasma RNA detection appears to be a promising approach for the development of gender- and polymorphism-independent fetal markers for prenatal diagnosis and monitoring. This development also opens up the possibility of non-invasive prenatal gene expression profiling by maternal blood analysis. Besides circulating DNA and RNA in plasma and serum, cell-free DNA in other body fluids, such as urine, has been detected in patients with different clinical conditions. Regardless of the sources of cell-free DNA for clinical use, the amount is frequently scarce. METHODS: Technical advancements in detecting free DNA have been made over the years. CONCLUSIONS: It is likely that further developments in the field of circulating nucleic acids will provide us with new diagnostic and monitoring possibilities over the next few years.

DNA↗
PubMed2005

Circulating interleukin-18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis.

BACKGROUND: T helper type 1 (Th1) responses have been implicated in the protective immunity, pathophysiology and development of tuberculosis. However, it is still unclear which molecule(s) reflect disease activity in patients with tuberculosis. METHODS: By specific enzyme immunoassays, circulating interferon-gamma. (IFN-gamma), interleukin-12 (IL-12), IL-18 and osteopontin (OPN) were measured in 47 patients with pulmonary tuberculosis and 7 patients with miliary tuberculosis before anti-tuberculosis therapy, and also measured in 19 patients with tuberculosis before and after anti-tuberculosis therapy. RESULTS: Circulating IFN-gamma, IL-18 and OPN levels were significantly higher in patients with pulmonary tuberculosis than in healthy controls, while there was no significant difference in levels of circulating IL-12 between tuberculosis patients and controls. Circulating IFN-gamma, IL-12, IL-18 and OPN paralleled the extent of lung lesions, and circulating IFN-gamma, IL-18 and OPN paralleled the magnitude of fever in patients with pulmonary tuberculosis. Patients with miliary tuberculosis had extremely high levels of circulating OPN, IFN-gamma and IL-18. Circulating IL-18 and OPN were significantly decreased with anti-tuberculosis therapy, whereas circulating IL-12 and IFN-gamma were not. CONCLUSIONS: Among Th1 response associated molecules, circulating levels of IL-18 and OPN, but not IFN-gamma or IL-12, reflect disease activity in patients with tuberculosis.

Adult↗