Increase In Acute Phase Reactants Research Articles

Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) represents a group of lung disorders caused by the inhalation of a wide variety of organic particles by susceptible individuals. HP occurs mainly in nonsmokers, but smoking may promote an insidious and chronic disease. The prevalence of HP is difficult to estimate accurately since several antigens can produce the disease, but the range spans infancy to old age. Regardless of the causative antigen or its environmental setting, the clinical manifestations are essentially the same. Three different clinical presentations have been recognized: acute, subacute, and chronic. In the acute form, patients show flu-like symptomatology, followed by dyspnea and dry cough. Symptoms subside a few hours or days later. The subacute and chronic forms result from recurrent low-level antigen exposure and are characterized by progressive dyspnea and dry cough. Other constitutional symptoms such as fatigue, anorexia, and weight loss can be apparent. Fever may occur in the subacute form. Importantly, chronic HP may evolve insidiously or may result from repeated acute/subacute episodes. Recurrent acute, subacute, and chronic HP may progress to irreversible lung fibrosis or provoke emphysematous changes.HP can be difficult to identify, and precise diagnosis requires a history of exposure and a constellation of clinical, imaging, laboratory, bronchoalveolar lavage and pathologic findings. General laboratory tests show an increase of acute phase reactants. Specific precipitating antibodies, when present, are evidence of antigen exposure, and are a hallmark for diagnosis. Chest radiograph usually reveals widespread ground-glass attenuation, and nodular or reticulonodular shadowing. High-resolution CT features include diffuse or patchy ground-glass opacities with small poorly defined nodules and air trapping. Pulmonary function tests are characterized by a predominantly restrictive ventilatory defect with loss of lung volume and hypoxemia at rest that worsens with exercise. Bronchoalveolar lavage reveals a significant increase in lymphocytes, mostly over 40%. In the acute form there is also an increase in neutrophils. Antigen-induced lymphocyte proliferation, and environmental or laboratory-controlled inhalation challenge, may be used for diagnostic purposes and can help to establish a diagnosis of insidious forms of HP. In subacute or chronic cases, lung biopsy may be necessary. Typical findings include bronchiolitis, lymphocytic alveolitis, and loosely formed granulomas, although occasionally other morphologic patterns such as nonspecific interstitial pneumonia may exist. Treatment focuses on avoiding further exposure to the offending antigen(s). Corticosteroids are recommended in subacute and chronic forms. The usual regimen consists of initial high doses of systemic corticosteroid (e.g. prednisone 0.5-1.0 mg/kg/day), followed by gradual tapering.

Cholesterol emboli syndrome in type 2 diabetes: the disease history of a case evaluated with renal scintigraphy.

Cholesterol crystal emboli syndrome (CCE) is an emerging disease, whose progression reflects the currently observed increase in cardiovascular diseases. Diagnostic criteria shifted from pathological to clinical criteria: creatinine increase, skin lesions, recent endovascular interventions and severe vasculopathy). Diabetes, hypertension and diffuse vascular disease are inter-linked, major risk factors. The role of imaging techniques in the diagnosis and treatment of the disease has been little investigated thus far. The AIM of this report is to describe a case exemplifying the potentials for renal scintigraphy in CCE, an emerging disease in type 2 diabetic patients. A 75 year-old, type 2 diabetic for over 15 years, obese, hypertensive white man was referred to the Nephrology Unit after an acute coronary syndrome. Stenosis of the left renal artery was diagnosed from the angiography. Serum creatinine (baseline: 1.9 mg/dl) increased after multiple angioplasties to 3.3 mg/dl, then slowly returned towards baseline (2.2 mg/dl), but rose, on referral, to 3.9 mg/dl, with an increase in acute phase reactants and peripheral livedo reticularis, a picture highly suggestive of CCE. The first renal scintiscan showed a reduction of the parenchymal phase, and a non-homogeneous parenchymal pattern in the right dominant kidney. The patient was started on corticosteroid therapy with a prompt decrease in creatinine; four days later (creatinine 2.5 mg/dl) a second scintiscan showed an improvement of the peak time and of the radionuclide parenchymal transit, and was further confirmed two months later (creatinine 2.2 mg/dl). No modification was detected in the left kidney, presumably mechanically "protected" from the cholesterol shedding by the stenosis. This is the first description of an imaging demonstration of the morpho-functional substratum to the rapid clinical response of corticosteroid therapy in a case of CCE and type 2 diabetes, underlining the potential of 99mTc-MAG3 dynamic scintiscan in this disease.

Acute myocardial infarction in young patients: nutritional status and biochemical factors

Purpose: The aim of this study was to establish whether nutritional status and biochemical factors, C-reactive protein (CRP), serum amyloid A (SAA) protein, serum iron (Fe) and fibrinogen at admission were different in patients with acute myocardial infarction (AMI) at a young age (<40 years) vs. those with AMI at an older age (>60 years). We also investigated whether during the stay in the hospital, the increase in acute-phase reactants was different in young vs. older subjects, and if dyslipidemic aspects were different between the two groups. Methods: The study population consisted of 40 patients, all males with a mean age of 36.7±1.16 years, admitted to our facility with AMI. The control group included 40 patients, all males, mean age of 66.3±4.24 years, with AMI. CRP, SAA, Fe and fibrinogen were determined at admission to the hospital and daily for 7 days in the two groups of patients. Results: In young patients the median value of the highest levels were 6.2 mg/l (range 0.7–27.30) for CRP, 13.22 mg/l (range 0.7–130) for SAA, 420 mg/dl (range 76–840) for fibrinogen and 49.1 gamma/ml (range 14–102) for Fe levels. In the older patients, the median value of the highest levels were 5.9 mg/l (range 0.6–28.30) for CRP, 12.12 mg/l (range 0.9–280) for SAA, 480 mg/dl (range 60–780) for fibrinogen and 47.1 gamma/ml (range 12–94) for Fe levels. Conclusions: In the present study, acute-phase reactants were quantitatively similar in young and old patients. On the contrary, nutritional status, homocysteine, LDL and triglycerides are significantly higher in young patients than in old patients.

Acute myocardial infarction in young patients: nutritional status and biochemical factors

Purpose: The aim of this study was to establish whether nutritional status and biochemical factors, C-reactive protein (CRP), serum amyloid A (SAA) protein, serum iron (Fe) and fibrinogen at admission were different in patients with acute myocardial infarction (AMI) at a young age (<40 years) vs. those with AMI at an older age (>60 years). We also investigated whether during the stay in the hospital, the increase in acute-phase reactants was different in young vs. older subjects, and if dyslipidemic aspects were different between the two groups. Methods: The study population consisted of 40 patients, all males with a mean age of 36.7±1.16 years, admitted to our facility with AMI. The control group included 40 patients, all males, mean age of 66.3±4.24 years, with AMI. CRP, SAA, Fe and fibrinogen were determined at admission to the hospital and daily for 7 days in the two groups of patients. Results: In young patients the median value of the highest levels were 6.2 mg/l (range 0.7–27.30) for CRP, 13.22 mg/l (range 0.7–130) for SAA, 420 mg/dl (range 76–840) for fibrinogen and 49.1 gamma/ml (range 14–102) for Fe levels. In the older patients, the median value of the highest levels were 5.9 mg/l (range 0.6–28.30) for CRP, 12.12 mg/l (range 0.9–280) for SAA, 480 mg/dl (range 60–780) for fibrinogen and 47.1 gamma/ml (range 12–94) for Fe levels. Conclusions: In the present study, acute-phase reactants were quantitatively similar in young and old patients. On the contrary, nutritional status, homocysteine, LDL and triglycerides are significantly higher in young patients than in old patients.

Familial mediterranean fever: revisiting an ancient disease.

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic attacks of fever and serositis. Recent genetic and epidemiological research have highlighted the importance of this disease. FMF is the most frequent periodic fever syndrome and is transmitted in an autosomal recessive fashion. The disease is caused by mutations in the gene on the short arm of chromosome 16, coding for the protein "pyrin". Pyrin is mainly expressed in neutrophils and monocytes and is among the proteins involved in the interleukin-1 inflammatory pathway. The recurrent attacks of fever are accompanied by severe abdominal pain, arthritis and/or chest pain along with a marked increase in acute phase reactants. Among these, serum amyloid A protein is especially important since it is the precursor of the amyloid A fibrils deposited in secondary renal amyloidosis. Renal amyloidosis has a grave prognosis. Differential diagnosis from other periodic fever syndromes is especially important in western European countries. Among these hyper IgD syndrome is common in Netherlands and the tumour necrosis factor receptor-associated periodic syndrome is especially common among Scottish and Irish families. Mutation analysis of the gene may be helpful in diagnosing FMF; however, if this is not possible, a trial of colchicine is a helpful diagnostic tool. The indications for life-long colchicine treatment should be discussed with the family. Familial mediterranean fever and other auto-inflammatory syndromes should be suspected in children with recurrent febrile attacks. Early diagnosis will save the child from unnecessary work-up and kidney involvement.

Tubulointerstitial nephritis and uveitis syndrome in Southern Spain

Objective: To examine immunogenetic and clinical features in a series of patients with the idiopathic tubulointerstitial nephritis and uveitis (TINU) syndrome diagnosed at the single referral hospital for a defined population in Southern Spain. Patients and Methods: Retrospective study of the case records of all patients diagnosed with the TINU syndrome in the Departments of Ophthalmology and Medicine of the Valme University Hospital (Seville, Spain) from January 1996 through October 2000. Patients were included in this study if they had a renal biopsy showing interstitial edema and infiltration by lymphocytes, plasma cells, macrophages, eosinophils, and neutrophils. In these cases fibrosis was occasionally seen, but no glomerular changes were found. In addition, a diagnosis of uveitis by expert ophthalmologists was always required. Underlying diseases, which might be responsible for the renal or ocular manifestations, were excluded. Patients were HLA-DRB1 genotyped from DNA by using molecular-based methods. Results: Six patients (4 females) fulfilled the definitions described above. Four were younger than 18 years. In addition to tubulointerstitial nephritis, non-granulomatous uveitis (anterior or panuveitis) associated with low visual acuity was present at the time of diagnosis. Leukocytosis and increase of acute phase reactants were also commonly observed at the time of diagnosis. Topical and oral corticosteroids were prescribed to all the patients. Cyclosporine A therapy was required in 2 cases. After a 2.5-year median follow-up, visual acuity had improved in all cases. Of note, 4 of 6 patients carried the HLA-DRB1*01 allele. Conclusion: The TINU syndrome should be considered in the differential diagnosis of patients presenting with visual and renal manifestations. The presence of renal dysfunction in patients with uveitis may be of some help, as a warning sign, for the recognition of patients who require a rapid diagnosis and therapy. In Southern Spain, the TINU syndrome appears to be associated with HLA-DRB1*01 allele. Semin Arthritis Rheum 32:125-129. Copyright 2002, Elsevier Science (USA). All rights reserved.

Nutritional Markers, Acute Phase Reactants and Tissue Inhibitor of Matrix Metalloproteinase 1 in Elderly Patients with Pressure Sores

Background: Loss of collagen and elastin is observed in the elderly. In geriatric inpatients, chronic protein malnutrition could induce susceptibility to additional morbidity such as pressure sores. Objective: The purpose of this study was to explore the relationship between nutritional and inflammatory status and the production of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). Methods: Chronically ill elderly inpatients, without or with pressure sores, were enrolled. Nutritional protein markers, acute phase reactants, and TIMP-1 were determined, and changes in these biological parameters were compared. Results: Chronic inflammatory process and protein malnutrition were observed in all enrolled patients. The severity of these two pathophysiological processes was independent of the occurrence of pressure sores. The serum prealbumin and albumin levels were lower in patients with pressure sores than in those without. In addition, the general increase in the TIMP-1 level was independent of the occurrence of pressure sores. The TIMP-1 level was mainly related to the prognostic inflammatory and nutritional index. Conclusions: The general increase in acute-phase reactants observed in the elderly could be related to the intercurrent diseases. The generally low serum albumin level, lowest in patients with pressure sores, may be considered evidence of protein malnutrition and hypercatabolism. Regarding the morbidity, the increase in TIMP-1 levels could be explained as an adaptive process to prevent intrinsic protein expenditure of extracellular matrices.

Systemic Inflammation Present in Patients Undergoing CABG Without Extracorporeal Circulation

This study was conducted to evaluate to what extent the cardiopulmonary bypass (CPB) procedure in patients undergoing coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response. Therefore, we measured bactericidal permeability increasing protein (BPI) as an indicator of neutrophil activation, interleukin 6 as inducer of the acute phase response, and lipopolysaccharide binding protein and C-reactive protein as parameters of the acute phase response in patients undergoing CABG either with or without the use of CPB. Prospective study. Cardiopulmonary surgery department in a university hospital. Sixteen patients undergoing elective CABG were included. Eight patients underwent surgery with CPB, and eight patients underwent surgery without CPB (non-CPB). In the CPB group, blood samples were taken upon induction of anesthesia, at the start of aortic cross-clamping, at aortic unclamping, and 0.5, 4, 8, and 18 h thereafter. In the non-CPB group, blood samples were taken upon induction of anesthesia, and 0.5, 4, 8, and 18 h after completion of the bypass graft anastomoses. BPI release from neutrophil granules markedly increased during surgery in CPB patients but not in non-CPB patients. The increase in acute phase reactants, however, was the same in both patient groups. These data indicate that the acute phase response in CABG patients, which has historically been ascribed to the CPB procedure, is predominantly caused by the surgical procedure per se. Early neutrophil activation, however, is seen only when extracorporeal circulation is used.

Substance P and stress-induced changes in macrophages.

The present paper further links nervous-endocrine-immune systems by describing influences of SP on the immune system, and more specifically, on macrophage function. We have discussed how macrophages are important to immune responses in that much of cellular and humoral responses depend on macrophage function. Macrophages are sensitive to stress in that cold-water stress causes increased cytokine production, either spontaneously (IL-1), or after induction with LPS (IL-6, TNF alpha). Increased cytokine levels (IL-1, IL-6) may induce acute phase reactants in the liver, which is presumably the mechanism operative in the studies indicating increases in acute phase reactants after certain stressors in animals. SP is a likely candidate to affect immune function. Previous data show that macrophages from various species have receptors for and respond to SP in vitro. SP stimulates phagocytic and chemotactic capacity, as well as increased cytokine, PGE2, and thromboxane B2 production. SP is also involved in neurogenic inflammation and is likely to be involved in the pathogenesis of several inflammatory diseases. Present data indicate SP's involvement in macrophage responses to stress. We have shown that stress induced differential SP receptor binding to peritoneal macrophages, although the precise nature of binding differences has not yet been clearly elucidated. Stress also induces more immunoreactive SP in the peritoneal fluid that bathes the peritoneal macrophages. We hypothesize that the two events, altered SP binding and concomitant increased ligand, are causally related. In addition to other correlational data showing concomitant increased SP binding plus ligand concentrations, there is more direct evidence that SP ligand may induce SP receptor expression since the SP antagonist, CP-96,345, prevents the induction of SP receptor mRNA in the staphylococcal toxin A-induced gastroenteritis (C. Pothoulakis and S. E. Leeman, personal communication). Further supporting our notion for a causal relationship we have found the elimination of SP in vivo (via capsaicin pretreatment) reduced SP binding, as has been previously reported. We have also examined the role of SP on stress-induced altered macrophage function in vitro. SP greatly enhanced the LPS-induced macrophage TNF alpha production from stressed animals; in contrast, it produced relatively little effect on macrophages from control animals. Capsaicin pretreatment diminished the enhanced cytokine production in response to stress, such that levels of TNF alpha and IL-6 approximated those of control mice. Taken together, past and present data suggest that (1) stress may initiate, or at least contribute to, an inflammatory response, and that (2) SP is involved in the macrophage stress response. SP has long been known to be involved in inflammatory processes; our data further suggest its role in mediating stress-induced cytokine alterations.

Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality.

Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflorescein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C-reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leukocytes from patients who died was significantly higher (P < 0.001) than paired controls, and greater (P < 0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte-derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.

Production of fever and its effects on the host.

Leukocytic pyrogen (LP) is a polypeptide that is released from phagocytic leukocytes and mediates fever, by direct action on the thermoregulatory centers in the hypothalamus. During the mediation a complex series of biochemical events occurs in the hypothalamus, including increases in prostaglandin synthesis. The production of LP by phagocytic leukocytes (predominantly monocyte/macrophage) requires synthesis of protein and new messenger-RNA. Recently, it has been discovered that LP has other direct effects on the host. Amongst these effects are: increases in acute phase reactants, including serum amyloid A protein (SAA); release of specific granule contents from neutrophils in vitro; a similarity (if not identity) to human lymphocyte activating factor (LAF) which is a monokine. Thus, LP may have a much broader role to play in the inflammatory response than just mediating fever.