Biological Markers Of Inflammation Research Articles

La gammagrafía con leucocitos marcados con 99mTc-HMPAO en el diagnóstico y seguimiento de la enfermedad inflamatoria intestinal

To assess the clinical value of 99mTc-HMPAO-leukocyte-labeled scintigraphy (LLS) in the detection and follow-up of inflammatory bowel disease (IBD) in the pediatric population, we retrospectively reviewed 33 patients (15 boys; mean age 10.7 +/- 2.2 years) with suspected IBD. A total of 58 examinations were performed: 29 for screening purposes, 23 for follow-up and 6 to detect relapses. LLS was compared with clinical symptoms (PCDAI index), biologic markers of inflammation, barium contrast radiology (BCR; n = 22), sonography (n = 22), colonoscopy (n = 16), and biopsy (n = 13). The final diagnosis was Crohn's disease in 12, ulcerative colitis in 4, and no IBD in 17. In the 17 patients without IBD, LLS was always negative. Among the 16 patients with IBD, LLS showed concordant results with BCR in 7/10 patients, with sonography in 6/11, with colonoscopy in 9/12 and with biopsy in 8/9. The severity of LLS increased with the PCDAI index (p < 0.001), with a positive correlation between the scintigraphic activity index/PCDAI r = 0.76. An increase in the PCDAI index with the severity of LLS (p < 0.001) was also observed in the follow-up, and a weak correlation (r = 0.50) between erythrocyte sedimentation rate/scintigraphic activity index was obtained. In 5 patients with normal biologic markers, LLS detected inflammation. All 6 patients with relapses were symptomatic; 5 had inflammation on LLS and 5 had abnormal biologic markers. In conclusion, LLS can be a useful screening tool in the detection of IBD in children to assess the grade of inflammation and extension of IBD. This technique can detect the presence of inflammation during follow-up and should be performed when relapses are suspected.

Correlation of severity of chronic venous disease with capillary morphology assessed by capillary microscopy

In patients with lipodermatosclerosis caused by chronic venous disease of the lower limb, the skin capillaries show proliferation and convolution. To our knowledge, no previous attempt has been made to correlate the clinical severity of venous disease based on the CEAP classification with the capillary morphology changes. The purpose of this study was to correlate the clinical severity with the capillary morphology changes in patients with chronic venous disease by using capillary microscopy and to explore the significance of atypical capillary morphology in patients with uncomplicated varicose veins. Patients attending the vascular clinic for management of chronic venous disease were examined clinically and by duplex ultrasonography scans, and they were assigned to the appropriate CEAP clinical stage (C1, n = 15; C2, n = 20; C3, n = 15; C4a, n = 15; C4b, n = 15; C5, n = 15). Also studied were 10 control subjects with no arterial or venous disease of the lower limb. In part 1 of the study, a capillary microscope was used to obtain digital images of the skin microcirculation in the gaiter region. The capillary density and capillary convolutions were counted in a 2.4 mm2 region of skin. In part 2 of the study, a further 33 C2 and C3 patients were studied to provide more detailed information on a small subgroup with unusual capillary morphology. In part 1 of the study, the capillary count was similar in controls and patients in CEAP stages C2 to C4a, but decreased in patients of groups C4b and C5 (median count: C2, 15; C4b, 4; and C5, 7). The median number of the capillary convolutions was 1 per capillary in patients of groups C1 to C3 and controls; C4a had 4 convolutions, C4b had 7, and C5 had > or = 10. In part 2 of the study, an expanded group of 66 C2 and C3 patients was analyzed, of whom 14 had a mean capillary loop count of more than two. Biologic markers of inflammation were investigated for their correlation with capillary convolution, but no relationship was found. Among patients with venous disease, increased capillary convolution is strongly associated with the more severe stages (lipodermatosclerosis and healed ulceration). The significance of atypically increased capillary convolutions in a small subgroup of C2/C3 patients remains unknown.

Pneumopathie organisée cryptogénique

Organising Pneumonia (formerly called Bronchiolitis Obliterans with Organising Pneumonia) is a particular form of inflammatory and fibroproliferative lung disease. Its idiopathic form called Cryptogenic Organising Pneumonia, was recently defined by an ATS/ERS consensus conference. The disease onset is subacute with cough, dyspnea, fever, asthenia, weight loss, crackles, and elevation of biological inflammatory markers. Bronchoalveolar lavage reveals a mixed alveolitis with elevated lymphocyte, neutrophil, and eosinophil counts. Chest imaging usually shows multifocal alveolar opacities predominating in the subpleural regions, often with a migratory pattern. Lung biopsy reveals budding connective tissue filling the distal airspaces. Diagnosis is established by combining clinical, radiological and histological criteria. Similarities with other disease processes can lead to delayed or erroneous diagnosis. Most patients respond well to corticosteroid therapy. Relapses are frequent but can generally be controlled with moderate doses of prednisone and do not worsen the prognosis. The therapeutic strategy aims at reducing the steroid doses while maintaining an optimal disease control.

Optimization of assay conditions for leukotriene B 4 synthesis by neutrophils or platelets isolated from peripheral blood of monogastric animals

Neutrophils are involved in inflammation through leukotriene (LT) production. The predominant proinflammatory leukotriene released from neutrophils is LTB 4, which serves as a biological marker of inflammation. The purpose of this study was to optimize the conditions ex vivo for LTB 4 production by neutrophils from horses and dogs, and platelets from chickens. Optimal production of LTB 4 was characterized by incubation time (2.5, 5, 10, 15 or 20 min), temperature (25 or 37 °C), and calcium ionophore A23187 concentration (0.1, 1, 10 or 20 μM). Incubation longer than 2.5 min did not increase production of LTB 4 in chickens or horses; in dogs, incubation for 2.5 and 10 min resulted in the highest concentrations of LTB 4 ( P ⩽ 0.05 ). In all species, incubation at 37 °C resulted in optimal LTB 4 production ( P ⩽ 0.05 ). Production of LTB 4 was highest when neutrophils or platelets were stimulated with 20 μM calcium ionophore in all species ( P ⩽ 0.05 ). These results indicate that neutrophils isolated from horses and dogs, and platelets isolated from chickens, are capable of producing LTB 4. Optimum conditions for LTB 4 production are similar in all three species.

Histamine and an H3/H4 receptor antagonist may modulate IgE and nitric oxide production

RATIONALE: Histamine and H3/H4 receptors may be involved in the regulation of IgE synthesis in atopic diseases. Nitric oxide (NO) is a biological marker of inflammation in asthma patients and NO production during asthma exacerbation increases. The aim of the present investigation is the evaluation of the role of histamine and H3/H4 receptors in IgE synthesis and NO metabolite production in asthma patients.

Valor pronóstico del fibrinógeno en pacientes ingresados con sospecha de angina inestable o infarto de miocardio sin onda Q

In recent years, the relation between biological markers of inflammation and prognosis in patients suffering from acute coronary syndromes has been investigated. The aim of this study was to evaluate the association between baseline fibrinogen concentrations and the development of clinical events in patients admitted with suspicion of unstable angina and non-Q-wave myocardial infarction. Levels of fibrinogen at enrollment were analyzed in 325 consecutive patients with acute coronary syndromes. Fibrinogen values were divided into tertiles and the incidence of clinical events was evaluated at each level. The combination of death and/or myocardial infarction was the main endpoint. Fibrinogen levels were significantly higher in patients who subsequently had myocardial infarction, cardiac death, or both during follow up. The probabilities of death and/or myocardial infarction were 6%, 13%, and 29% (p < 0.0001), respectively, in patients grouped by fibrinogen tertiles (304, 305-374 and 375 mg/dl). Multivariate predictors of combined events were age, previous angina, ST-segment depression in the admission ECG, and fibrinogen into tertiles. The adjusted hazard ratio (95% CI) for patients in the upper tertile was 4.8 (1.6-14; p = 0.004). High fibrinogen levels were related to a less favorable long-term or short-term outcome in patients admitted for suspicion of unstable angina and non-Q-wave myocardial infarction. This association persists after adjustment for other classical risk factors such as age, prior angina, and ST-segment depression in the ECG.

Use of biological markers of airway inflammation to detect the efficacy of nurse-delivered asthma education

Objective: The purpose of this study was to determine whether analysis of the constituents of induced sputum could be used to document the efficacy of a nurse-delivered patient education intervention and whether changes in the biological markers of inflammation in sputum would correlate with improvements in pulmonary function and symptoms. Design: The study design was prospective, open trial with repeated measures. Setting: The study took place at a West Coast academic medical center laboratory. Subjects: Subjects included 12 nonsmoking persons with asthma, ages 23 to 51 years, on prescribed daily anti-inflammatory inhaled therapy who had not required oral prednisone in the previous 4 weeks of enrollment. Method: The effect of one 30-minute asthma education session on spirometry, peak flow, symptoms, and biological markers of inflammation in sputum was tested for 8 weeks to determine whether biological markers reflect the efficacy of educational interventions. Results: Mean symptom scores decreased and lung function increased slightly over 8 weeks. Markers of eosinophil degranulation decreased by 50% and albumin by 25% from baseline to 8 weeks. Eosinophil percentages dropped 20% over time but did not change consistently at all time points. Clinical markers of asthma control correlated in the low-to-moderate range with biological markers of airway inflammation. Conclusion: The results of this study show the effects of a patient education intervention can be detected in both clinical and biological outcomes. Individual education may influence self-care of asthma including adherence to inhaled corticosteroid therapy and thereby suppress airway inflammation. (Heart Lung® 2001;30:39-46.)

Serum amyloid A--an indicator of inflammation in ankylosing spondylitis.

Biological markers of inflammation are useful for the diagnosis and monitoring of inflammatory rheumatic diseases. The present study tested, whether serum amyloid A (SAA) could be used as a marker of inflammatory disease activity in ankylosing spondylitis (AS). In 72 patients with AS, the two valuable surrogate markers of disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and an established clinical activity score (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI) were correlated to the serum levels of SAA. It was found that SAA correlates well with ESR, CRP, and BASDAI. Because of its strong correlation, SAA seems to be an additional very useful disease activity marker. When used in diagnosis, and especially in monitoring of inflammation, further studies are required. Another interesting point of view is the described role of plasma SAA as a precursor of Amyloid A (AA) protein in secondary amyloidosis, a known complication in AS. In all probability, high circulating SAA levels are a predisposing indicator of disease activity.

Protective role of nitric oxide-mediated inflammatory response against lipid peroxidation in ultraviolet B-irradiated skin.

Ultraviolet (UV) irradiation is known to induce serious oxidative damage in the skin via lipid peroxidation. Nitric oxide (NO) synthesized by keratinocytes, melanocytes and endothelial cells in response to proinflammatory cytokines and UV radiation, has been reported to prevent UV-induced apoptosis in the skin. We have examined the effects of NO on UVB-induced lipid peroxidation in murine skin in vivo. UVB induced a dose-dependent increase in lipid peroxidation of skin extracts in vitro; however, lipid peroxidation in the skin in vivo remained unaffected at irradiation doses of less than 1.0 J cm-2 and decreased significantly at doses over 1.5 J cm-2 (P < 0.01). Time-delayed inhibition of lipid peroxidation in the skin in vivo was observed after irradiation at 1.5 J cm-2. Administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced lipid peroxidation (P < 0.05), while it suppressed the ear-swelling response (ESR), a biological marker of inflammation. By contrast, administration of sodium nitroprusside, an NO enhancer, suppressed lipid peroxidation (P < 0. 01), while it enhanced the ESR. Expression of inducible nitric oxide synthase (iNOS) was observed from 12 to 48 h postirradiation at doses of 0.4-1.6 J cm-2. The UVB-induced iNOS expression was markedly inhibited by L-NAME, suggesting that iNOS is a major enzyme in the production of NO. These results suggest that NO acts as a mediator of the inflammatory response in UVB-irradiated skin, and that lipid peroxidation is inversely regulated with the NO-mediated inflammatory response in vivo.

The Antiinflammatory Effects of Aprotinin in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

Aprotinin has been shown to effectively attenuate cardiopulmonary bypass (CPB) induced coagulopathies. Because aprotinin is a serine protease inhibitor, it may exert additional properties that reduce the risks associated with extracorporeal flow. The purpose of this study was to prospectively evaluate the antiinflammatory effects of aprotinin with specific emphasis on pulmonary function. After Institutional Review Board approval, 20 patients undergoing first time coronary artery bypass grafting were randomly assigned to receive either a full dose regimen of aprotinin (APR, n=8), or volumetric equal control (CTR, n= 12). Biological markers of inflammation and coagulation were measured at 3 time periods: immediately prior to drug administration, at chest closure, and at 24 hours post cardiotomy, and included total complement, polymorphonuclear neutrophil (PMN) elastase, Factor XII, protein C, protein S, fibrin split products (FSP), D-dimers. Pulmonary function was assessed throughout intensive care unit (ICU) stay. There were no differences observed between groups in either preoperative, surgical, anesthesia or perfusion parameters. Twenty-four hour chest tube drainage in the APR group was significantly less than that observed in CTR patients (435.1±169.6 vs. 944.0±585.1, p&lt;.02). Patients receiving aprotinin received significantly lower transfusions of red blood cells, platelets, and fresh frozen plasma. Upon entry into the ICU the CTR group had significantly higher mean airway pressures (8.3±1.5 vs. 10.8±2.9 em H2O, p&lt;.03), higher PaCO2 levels (37.1±4.8 vs. 43.3±7.1 mmHg, p&lt;.04), and higher FIO2 settings (0.63±0.18 vs. 0.75±0.20, p=.l6). Postoperative FSP and D-dimers were significantly lower in the APR treated patients. In conclusion, the use of aprotinin resulted in significant improvements to postoperative patient outcomes as assessed by transfusion requirements, blood loss, coagulation markers and pulmonary function.

Schönlein-Henoch purpura in adult patients. Predictive factors for IgA glomerulonephritis in a retrospective study of 57 cases.

To evaluate the incidence of extracutaneous manifestations and to identify predictive factors for renal involvement in adult patients with Schönlein-Henoch purpura. Retrospective study with a comparative analysis of patients with and without renal involvement. Patients who were attending the dermatologic department of an academic medical center. In patients with purpura of the lower limbs and cutaneous vascular IgA deposits for which cases were recorded from 1985 to 1993, the following selection criteria were used: age older than 15 years and absence of thrombocytopenia, of IgA deposits in the basement membrane zone, and of a known hematologic or connective tissue disorder. Clinical and biological data, results of histological studies, and findings from direct immunofluorescence studies of skin biopsy specimens were compared in patients with and without renal involvement. Fifty-seven patients were included: 23% had an IgA glomerulonephritis confirmed by results of a renal biopsy, and a further 26% showed abnormalities on urine microscopy. Joint and gastrointestinal involvement was noted in, respectively, 33% and 19% of the patients. A comparative analysis of patients with and without renal involvement failed to reveal significant differences with regard to age, sex, the presence of bullous or necrotic cutaneous lesions, gastrointestinal or joint involvement, histological features, and findings from direct immunofluorescence studies. An IgA glomerulonephritis was significantly associated with purpura above the waist (P = .03), a recent infectious history (P = .02), pyrexia (P = .01), and biological markers of inflammation (P = .006). Despite a lower incidence of systemic involvement compared with that in other published series, the incidence of renal involvement remained high (ie, between 23% and 49%). A recent infectious history, pyrexia, the spread of purpura to the trunk, and biological markers of inflammation were predictive factors for renal involvement.

Modification of inflammatory processes by phenobarbital in rats

Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this biological marker of inflammation or is capable of altering the clinical course of inflammatory processes. Local carrageenan injection induces a similar time-dependent plantar edema and increases serum AGP levels in Sprague-Dawley (SD) and Dark Agouti (DA) rats. Pretreatment with PB for seven days modified neither parameter in SD rats while plantar edema was aggravated and serum AGP levels were increased in DA rats. The sedative-hypnotic properties of PB were not involved, since a single administration of this drug had no action in DA rats. On the other hand, chronic PB administration reduced the severity of an autoimmune disease, type II collagen-induced arthritis, in DA rats. These data indicate that PB, a potent inducer a cytochrome P-450-dependent enzymes, modifies the course of the inflammatory process. Preliminary results with macrophage transfer experiments suggest that this response to PB could be mediated by stimulated macrophages.

Biological Markers of Inflammation and Carpal Tunnel Syndrome in Dialysis Patients

Biological Markers of Inflammation and Carpal Tunnel Syndrome in Dialysis Patients