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PubMedDate not supplied

The circulating insulin-like growth factor system in children with coeliac disease: an additional marker for disease activity.

BACKGROUND: Chronic undernutrition resulting from coeliac disease (CD) could be associated with changes in the circulating insulin-like growth factor (IGF) system, which may participate in the pathogenesis of growth retardation occurring in these patients. METHODS: We performed a cross-sectional study in CD subjects attempting to (1) document the pattern of serum IGF-I and IGF binding protein (IGFBP) 1 and 3 at diagnosis and (2) assess the response of circulating IGF system to dietary treatments, in comparison with the response of clinical and laboratory findings utilized for the diagnosis of CD. Thirty-two prepubertal CD children were divided into three groups based on the dietetic treatment: at diagnosis (D, n=18); on gluten-free diet for at least 6 months (GFD, n=7); and on gluten challenge for at least 3 months (CH, n=7). Six postpubertal CD patients were also studied at diagnosis. RESULTS: In prepubertal children IGF-I levels were significantly reduced (by 29%) in D vs sex- and age-matched normal control (NC) subjects, with reductions being more pronounced before 3 years of age. Likewise, serum IGFBP-3 concentrations were decreased by 22%, whereas circulating IGFBP-1 levels were increased by 60%, compared with NC, with more marked IGFBP changes in older children. Similar alterations were observed in postpubertal patients. Changes in the circulating IGF system disappeared in GFD subjects and reappeared in CH children, as positivity of disease-specific antibodies. Body mass index (BMI) also improved in GFD subjects, but did not decrease in CH children. Changes in IGF-I and IGFBPs did not correlate with each other. Levels of IGF-I, but not of IGFBPs, maintained the relation with age and correlated significantly with BMI and positivity of antibodies. CONCLUSIONS: These results demonstrate that CD patients show significant changes in serum IGF-I, in younger children, and IGFBPs (particularly IGFBP-1), in older children and adolescents, correlating with clinical course and response to dietary treatments. The alteration in the circulating IGF system could be implicated in the pathogenesis of growth retardation occurring in CD and may provide an additional tool in monitoring of the disease.

Autoantibodies↗
PubMed1990

Properties of the exchangeable splenic platelets released into the circulation during exercise-induced thrombocytosis.

The human spleen normally retains about one-third of the body's platelets in an exchangeable pool which can be released into the circulation by alpha-adrenergic stimulation. Some previous investigators concluded that the splenic platelet population was enriched in a subpopulation of large, young, dense platelets (megathrombocytes) but more recent research suggests that platelet size, age, and density are largely independent variables. In this investigation the properties of the splenic platelets were studied after their release into the circulation by acute strenuous exercise in 11 normal subjects. The exercise caused a rise in mean platelet count from 245 +/- 49 to 328 +/- 71 x 10(9)/L--a net increase of 24 +/- 6% after correction for haemoconcentration. The mean platelet volume (MPV) of citrated platelets increased from 6.38 +/- 0.78 to 6.59 +/- 0.68 fL after exercise (P less than 0.01)--a rise of 3.7 +/- 4.1% suggesting that the MPV of the splenic platelet population was about 20% greater than that of the normal circulating population. The age distribution of the platelets was studied by measuring the platelet monoamine oxidase (MAO) activity several days after irreversible inhibition by tranylcypromine, when the young platelets had normal MAO activity but the older platelets had only 20% of normal activity. The mean platelet MAO activity did not change after exercise, indicating that the age distributions of the circulating and splenic populations were very similar. The platelet contents of several putative markers of platelet age (sialic acid, serotonin, beta-thromboglobulin, beta-N-acetylglucosaminidase) were also unchanged after exercise. Modal platelet density decreased slightly but not significantly after exercise. The splenic platelet population has a larger MPV but appears to have similar age and density distributions to the basal circulating population.

Adult↗
PubMed2002

Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma.

BACKGROUND: The aim of the current study was to assess circulating levels of endogenous endostatin in patients with renal carcinoma and to determine the relationship of these levels to circulating levels of vascular endothelial growth factor (VEGF) and prognosis. METHODS: The authors prospectively studied 66 patients (48 male, 18 female; mean age, 50 years) undergoing nephrectomy for renal carcinoma on clinical trials at the National Cancer Institute. Metastases were present in 51 of 66 patients (77%) at the time of nephrectomy. Preoperative and followup serum endostatin and VEGF levels were determined using competitive enzyme immunoassays and compared to a group of 32 age- and gender-matched healthy controls. Associations between circulating endostatin levels and clinicopathologic variables, including survival, were determined. RESULTS: Preoperative endostatin levels were higher in renal carcinoma patients than in healthy controls (P = 0.05). There was a weak to moderate correlation between pretreatment serum endostatin levels and serum VEGF levels (r = 0.47; P = 0.001), and levels of both proteins increased significantly following nephrectomy (P < 0.0001 and P < 0.0001, respectively; n = 41). In addition, patients whose endostatin levels increased more than twofold after nephrectomy had significantly poorer prognoses than patients without such an increase (P = 0.018). This association was more pronounced when patients without metastases were excluded (P = 0.0037). CONCLUSIONS: Circulating endostatin levels are elevated in patients with renal carcinoma and correlate with circulating VEGF levels. Endostatin levels increase after nephrectomy, and patients with the greatest increases experience shortened survival times. These findings suggest an association between tumor aggressiveness and the production of endogenous endostatin in patients with renal carcinoma.

Adult↗
PubMed1994

Cross-linked bispecific monoclonal antibody heteropolymers facilitate the clearance of human IgM from the circulation of squirrel monkeys.

We have previously demonstrated that cross-linked bispecific monoclonal antibodies (mAb) heteropolymers (HP), specific for primate erythrocyte (E) complement receptor type 1 (CR1) and target antigen (Ag), facilitate the binding of these target Ag to human and non-human primate E. Once bound in vitro to rhesus monkey E, upon re-infusion these HP/Ag complexes are recognized in vivo by cells of the reticuloendothelial system (RES) and removed from the circulation without loss of the E. We now show, in squirrel monkeys, that an HP specific for E CR1 and human IgM (anti-CR1 x anti-IgM) can be used to facilitate in vivo E binding and clearance from the circulation of a previously injected and circulating model protein pathogen, human IgM. Approximately 70-80% of 125I-labeled human IgM is cleared from the circulation of each of five squirrel monkeys via the HP system. We observe, in experiments analogous to previous studies on immune complex (IC) clearance, that subsequent to HP/Ag clearance there is a decrease in the number of CR1 epitopes per E which is manifested when we use both monoclonal and polyclonal anti-CR1 probes. Our results indicate that the primary organs responsible for uptake of the complexes are the liver and spleen. This work strongly suggests that the HP/Ag complexes, bound to E, function as IC prototypes and are recognized and processed as such in vivo. Thus, the HP-E system may eventually serve as a viable immunotherapy for the clearance of blood-borne pathogens from the circulation.

Animals↗
PubMedDate not supplied

Hepatobiliary clearance of IgA immune complexes formed in the circulation.

The formation and clearance of circulating IgA immune complexes from blood to bile was investigated in this study. The i.v. injection of either MOPC-315, an IgA M-component with antidinitrophenyl (DNP) specificity, or TEPC-15, an IgA M-component of a different specificity, was followed by i.v. injection of 125I-DNP10-bovine serum albumin (BSA) as the antigen. The formation and clearance of IgA immune complexes in the circulation of MOPC-315-treated, but not TEPC-15-treated animals was demonstrated by immunoprecipitation with polyacrylamide beads coated with rabbit anti-mouse IgA. IgA-125I-DNP10-BSA complexes were identified in the bile from MOPC-315-treated, but not TEPC-15-treated animals utilizing this same immunoprecipitation technique. These observations suggest that the liver or bile ducts transport IgA immune complexes from blood into bile. The clearance of 125I-DNP10-BSA from the circulation was documented by coprecipitation with rabbit anti-BSA and BSA. The clearance of this circulating antigen was slower in the MOPC-315-treated than in the TEPC-15-treated animals suggesting that under the conditions of the present experiment, circulating antigen is cleared more slowly after IgA immune complex formation.

Animals↗
PubMedDate not supplied

Elevated circulating immune complexes in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology characterized by an association with inflammatory bowel disease in 50% or more cases. Since altered immunity, including circulating immune complexes, has been implicated in the pathogenesis of inflammatory bowel disease, we postulated that humoral immune mechanisms might also be important in the development of PSC. Therefore, as an initial step in testing this hypothesis, we examined sera of patients with PSC for the presence of circulating immune complexes by two independent methods: C1q binding and Raji cell assays. Twenty-four patients with PSC, 16 of whom had coexisting chronic ulcerative colitis, were prospectively selected by predefined biochemical, histologic, and radiographic criteria. Sixteen patients with inflammatory bowel disease and normal liver tests as well as six patients with extrahepatic biliary obstruction served as disease controls. Sera were positive for circulating immune complexes by at least one method in 80% (16/20) of patients with PSC; 70% (14/20 were positive by the Raji cell assay, 58% (14/24) by the C1q binding assay, and 45% (9/20) by both methods. Levels of circulating immune complexes by each assay were higher in sera from patients with PSC than in sera from healthy controls or patients with inflammatory bowel disease alone (p less than 0.01). There were no differences in the levels of circulating immune complexes or in the frequency of positive tests in PSC patients with or without associated inflammatory bowel disease. In addition, there was no difference between the Raji cell binding of sera from six patients with extrahepatic biliary obstruction and six healthy controls tested concurrently. These data are consistent with the hypothesis that immunologic mechanisms may be important in the pathogenesis of PSC.

Antigen-Antibody Complex↗
PubMed1990

Identification of virus components in circulating immune complexes isolated during hepatitis A virus infection.

Circulating immune complexes were isolated by conglutinin affinity chromatography during the course of hepatitis A virus infection in a chimpanzee. Characterization of circulating immune complexes showed that most of the hepatitis A virus-specific antibody was IgM, that IgG was present and that C3d and fibronectin were also present. Hepatitis A virus capsid polypeptides were identified in the circulating immune complexes and polypeptides in the molecular weight range of 63 to 67 kDa having immunological determinants common to both C3d and hepatitis A virus. Hepatitis A virus-RNA was detected in these circulating immune complexes using the polymerase chain reaction for in vitro amplification of nucleic acid and suggests the circulating immune complexes contain intact virus.

Animals↗
PubMed2006

Significance of circulating endothelial progenitor cells in hepatocellular carcinoma.

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC.

Adult↗
PubMed1987

Ganglionic circulation and its effects on neurons controlling cardiovascular functions in Aplysia californica.

The abdominal ganglion of the mollusk Aplysia californica receives most of its blood supply through a small caudal artery that branches off the anterior aorta near its junction with the heart. Injection of an ink/gelatin mixture into the caudal artery revealed a consistent pattern of arterial branching within the ganglion and a general proximity of larger vessels to identified neurons controlling circulation in this animal. This morphological arrangement was particularly evident for the heart excitor interneuron, cell L10, which lies next to the caudal artery near its entry into the ganglion. In electrophysiological experiments, L10 was excited when blood flow or oxygen tension within the ganglion was reduced. This effect was expressed as a gradual increase in impulse frequency of L10 and conversion from tonic to bursting mode of spike discharge. L10 follower cells in the RB and LD neuron clusters were affected synaptically by the changes in L10 activity, while other follower cells (L3 and RD neurons) responded independently of L10's synaptic influence. The neurosecretory white cells (R3 to R14) that innervate the major arteries and pericardial tissues were also excited when ganglionic circulation was interrupted. In innervated preparations of the heart and respiratory organs, decreased circulation through the abdominal ganglion stimulated a transient increase in the rate and amplitude of respiratory (gill) pumping and pericardial contractions and caused a sustained increase in activity of the heart. Both responses increase cardiac output and both appear to involve a direct influence of ganglionic circulation on interneurons controlling the gill and heart. These results indicate that the cell-specific patterns of excitation and inhibition caused by fluctuations in ganglionic circulation may be important factors for maintaining circulatory homeostasis in this animal.

Animals↗
PubMed1999

Fates and vascular action of S-nitrosoglutathione and related compounds in the circulation.

To know the metabolism of low-molecular-weight S-nitrosothiols (RS-NO) in the circulation, we analyzed the stability and depressor effects of S-nitrosoglutathione (GS-NO) and the l- and d-forms of S-nitrosocysteine (Cys-NO). Although half-lives of these RS-NO in fresh plasma were longer than 50 min, their depressor effects disappeared within 5 min after intravenous administration of these compounds. Acivicin (AT-125), an inhibitor of gamma-glutamyltransferase (gamma-GTP), prolonged the depressor effect of GS-NO but not of Cys-NO. The depressor effect of GS-NO disappeared in AT-125-treated rats within 10 min after administration, which is still shorter than its half-life in vitro. Although S-conjugates of l-cysteine, but not of d-cysteine, rapidly enter into cells via an active transport system and disappear from the circulation, both forms of Cys-NO exhibited similar activity to decrease blood pressure to that of NO. Thus, NO might be rapidly released from Cys-NO in the circulation and shortly exhibited its depressor action. These observations suggested that the circulating GS-NO is rapidly decomposed by gamma-GTP to form Cys-NO and that the release of NO from both GS-NO and Cys-NO is enhanced significantly in the circulation.

Acetylcysteine↗
PubMed1997

Ontogenic changes in the circulating concentrations of insulin-like growth factor (IGF)-I, IGF-II, and IGF-binding proteins in the chicken embryo.

The ontogeny of circulating concentrations of insulin-like growth factor (IGF-)-I, IGF-II, and IGF-binding proteins (IGF-BPs) was examined in the chick embryo. Distinct ontogenic changes in the circulating concentrations of IGF-I and IGF-II were observed. The present study confirms the overall profile for circulating concentrations of IGF-I. During middevelopment, plasma concentrations of IGF-I increased to a maximum which was attained on Day 14.5 of incubation. Thereafter, plasma concentrations of IGF-I declined with decreases (P < 0.05) between Days 14.5 and 15.5 and between Days 16.5 and 17.5 of incubation. In contrast to the monophasic profile for IGF-I, plasma concentrations of IGF-II were maximal on Day 10.5 of incubation and declined to a nadir on Day 17.5 of incubation. In late developmental stages (17.5 or 18.5 days of incubation), three IGF-BPs, having molecular weights of 22, 28, and 36 kDa, were detected in the plasma of chick embryos. No significant ontogenic changes in the circulating levels of the 28- and 36-kDa IGF-BPs were observed. However, it should be noted that prior to Day 17.5 of incubation, the 22-kDa IGF-BP was nondetectable in the circulation. The role of these changes in the functioning of IGF in embryonic development is discussed.

Animals↗
PubMed2000

The effects of photoperiod and feeding on the diurnal rhythm of circulating thyroid hormones in the red drum, Sciaenops ocellatus.

Available data in cyprinid and salmonid species indicate that nutrient intake sustains thyroidal rhythmicity and that time of feeding may influence the amplitude, but not the phase, of diurnal thyroid hormone cycles. Several experiments were conducted to characterize the nature of thyroidal rhythmicity in a more derived perciform teleost, the red drum. These studies were designed to test the following hypotheses: (1) that feeding time will alter the amplitude of the thyroid hormone rhythm without altering its phase and (2) that food deprivation will diminish the amplitude of the thyroid hormone rhythm. Circulating T(4) levels in this species exhibit high-amplitude diurnal rhythms, whereas circulating T(3) levels fluctuate within a more narrow range. Fish were reared under a 12L:12D photoperiod and fed 5% body weight once daily either at dawn or at dusk. Feeding time had no discernible effect on the phase of the T(4) cycle, but altered the amplitude of the cycle. Dawn-fed fish had significantly greater mean peak levels of T(4) than dusk-fed fish, although there was no difference in daily mean levels in both groups of fish. When red drum were deprived of food, significant declines in plasma glucose, HSI, and liver glycogen content occurred within 3 days. When red drum were sampled once per day after 3, 7, or 11 days of food deprivation there were no consistent changes in circulating T(4) and T(3) levels compared to those of fed controls. However, significant declines in circulating T(4) and T(3) levels in response to food deprivation were detected with a diurnal sampling protocol. Within 3 days of food deprivation, T(4) levels were significantly reduced compared to those in fed controls and not significantly different from T(4) levels after 10 days of food deprivation. T(3) levels exhibited a stepwise decline in circulating levels during food deprivation. These data indicate that both feeding time and nutrient status exert their effects on thyroid hormone rhythms by modifying the amplitude of these cycles. These data also underscore the importance of incorporating a consideration of endocrine rhythmicity into sampling protocols.

Animals↗
PubMed1993

Circulating alpha-actin in angina pectoris.

We used Western blot, a highly sensitive technique that detects amounts of protein as low as 0.1 to 1.0 ng, to investigate the possible presence in the blood stream of the contractile protein alpha-actin in 29 patients diagnosed with angina pectoris (Braunwald's classification). Circulating protein was identified with a monoclonal antibody specific for cardiac alpha-actin. Of the 20 control samples of blood, the immunoblot results were negative for alpha-actin in 19. Of the 30 patients with skeletal muscle damage caused by surgery, 27 were negative for circulating alpha-actin. Of the 29 patients with angina pectoris, circulating alpha-actin was found in 19 as a 43 kDa band in immunoblots. Of the four patients with anterior acute myocardial infarction, mean concentration of circulating alpha-actin was 58 mg/l. Among the patients with angina pectoris, the highest circulating concentrations (mean 40 mg/l) was found in those with prolonged angina (class III B, according to Braunwald's classification). In the entire group of individuals with angina pectoris alpha-actin was detectable in serum for up to 175 h after the onset of pain, and showed two peaks, one at 1 h (112 mg/l) and one at 50 h (82 mg/l) after the onset of pain. These findings reinforce the notion that unstable angina should be considered a serious condition.

Actins↗
PubMed1983

Circulating immune complexes in malignant diseases increased detection rate by simultaneous use of three assay methods.

By using three different assay methods, circulating immune complexes have been detected in 85% of sera from patients with malignant melanoma, and in 77% of sera from patients with breast cancer. These methods were a C1q-binding assay, a double-antibody conglutinin-binding ELISA, and a polyethylene glycol 6000 precipitation technique followed by quantitative determination of immunoglobulins in the redissolved precipitate. Detection rates of circulating immune complexes using any one of these methods separately ranged from 33% to 56%, indicating the presence of different types of circulating immune complexes in cancer patients' sera. The combined use of the three methods mentioned resulted in an increased diagnostic sensitivity and a doubling of the predictive value. However, tests for circulating immune complexes cannot be considered as useful parameters for early diagnosis of cancer, since the comparatively low incidence of malignancies in the population at large, together with the presence of circulating immune complexes in other, nonmalignant, diseases of considerable prevalence, appears to preclude effective application of any nonspecific method for early diagnosis of cancer in general.

Antigen-Antibody Complex↗
PubMed1981

CSF circulation in subjects with the empty sella syndrome.

The etiology to the empty sella syndrome (ESS) is not known. Increased intracranial pressure (ICP) has been suggested to be one of the possible causes. In the present study the CSF circulation was analyzed in 48 subjects with ESS with gamma cisternography, pneumoencephalography (PEG) and computed tomography (CT). In 80% of the subjects the CSF circulation was retarded with convexity block which was combined with widened CSF transport pathways and basal cisterns. These findings were correlated with the clinical signs and symptoms, most of which seemed to be related to the imparied CSF circulation (i.e. impared memory, balance disturbances, cerebellar ataxia, papilledema, hypertension and pituitary disorders). Headache, psychiatric symptoms, visual field defects and obesity, however, were not related to the impaired CSF circulation. It is concluded that impaired CSF dynamics leading to intermittent increase of ICP has a major impact on the development of the ESS and that most of the patients' complaints are related to this disturbance. Thus it is important to obtain information of the CSF dynamics concurrent with the diagnosis of ESS. For this purpose PEG or CT may be used as the first examination. Moreover, the patient should be examined at least every second year for symptoms and signs of progressive impairments of the CSF circulation.

Adolescent↗
PubMedDate not supplied

Alterations in circulating cyclic guanosine monophosphate (c-GMP) during short and long ischemia in preconditioning.

The aim of this study was to investigate if levels of circulating cyclic guanosine monophosphate (c-GMP) alter in preconditioning. Twenty-eight rabbits were divided into four groups. In vivo hearts were preconditioned, either with 5 min (group A, n = 8) or with 1 min (group B, n = 8) ischemia, followed by 10 min reperfusion, while groups C (n = 7) and D (n = 5) had no interventions. Protection was determined by subjecting groups A, B and C (but not D) to 30 min regional ischemia which was followed (including group D) by 2 h reperfusion. Seven blood samples were collected for the assessment of circulating c-GMP at different points of time. All results were expressed in pmol/ml using radio-immunoassay and the infarcted to risk area in percent using fluorescent particles and tetrazolium chloride (TTC). Circulating c-GMP increased during long ischemia only in group A (baseline value 47 +/- 4, long ischemic values 60.5 +/- 4 and 60.4 +/- 4, p < 0.05). Circulating c-GMP in group A was significantly higher in the middle of the long ischemia in comparison to the groups B, C and D (60.5 +/- 4 vs 43.9 +/- 4, 45.8 +/- 5 and 43.6 +/- 4, p < 0.05). Infarcted to risk ratio was lower in group A than in groups B and C (12.2 +/- 4 vs 29.6 +/- 6 and 34.2 +/- 6 respectively, p < 0.05). Circulating c-GMP is increased in classically preconditioned in comparison to ineffectively preconditioned hearts or to control groups. This elevation may be related to the protective effect of this phenomenon.

Animals↗
PubMed1994

Circulating concentrations of interleukin-6 in cancer patients and their pathogenic role in tumor-induced hypercalcemia.

Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P < 0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.

Adult↗
PubMed1995

Circulating neutrophils from patients with ulcerative colitis have a normal respiratory burst.

The hallmark of ulcerative colitis is a diffuse infiltration of neutrophils from the circulation into the colonic mucosa. The underlying mechanism for neutrophil tissue infiltration is unknown. One possible hypothesis is abnormal circulating neutrophils. This hypothesis has been previously tested with conflicting results. The aim of our study was to re-evaluate circulating neutrophil function in the absence of several possible confounding factors. To this end, we measured the respiratory burst of circulating neutrophils in response to two different stimuli by chemiluminescence in patients with active and inactive ulcerative colitis being off all medications. Our results show no significant difference between ulcerative colitis patients and controls in peak chemiluminescence, area-under-the-curve and time to peak comparisons. However, 27% of patients with active ulcerative colitis had an abnormally elevated chemiluminescence to stimuli. In addition, no correlations were seen between disease activity and peak chemiluminescence. Thus circulating neutrophils in the majority of patients with ulcerative colitis do not appear to be either "primed" or hyperactive. This may suggest the presence of local colonic factors that lead to neutrophil tissue infiltration and activation.

Adult↗