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PubMed1994

Microalbuminuria in inflammatory bowel disease.

Microalbuminuria independently predicts the development of nephropathy and increased cardiovascular morbidity and mortality in diabetic patients, but it may be an indicator of the acute phase response. This study examined microalbuminuria as a marker of the acute phase response in patients with inflammatory bowel disease and correlated it with the disease activity in 95 patients with inflammatory bowel disease (ulcerative colitis (n = 52), Crohn's disease (n = 43)) determined by the simple index of Harvey and Bradshaw. Fifty patients were in complete clinical remission and 45 patients had active disease. Microalbuminuria was detected in all patients with inflammatory bowel disease (147 (17) v 18 (2) microgram/min, inflammatory bowel disease v controls mean (SEM), p < 0.007). Patients with active inflammatory bowel disease had higher concentrations of microalbuminuria compared with patients in remission (206 (19) v 65 (8) microgram/min, mean (SEM), p < 0.0001). Eight patients with active inflammatory bowel disease who were sequentially followed up with measurements of microalbuminuria had significantly lower values, when the disease was inactive (active inflammatory bowel disease 192 (44) v inactive inflammatory bowel disease 64 (14) microgram/min, p < 0.03). There was a significant correlation with the simple index of Harvey and Bradshaw (r = 0.818, p < 0.0001). Microalbuminuria values were significantly lower in inflammatory bowel disease patients in remission, maintained with olsalazine compared with those patients maintained with mesalazine and salazopyrine, but no significant difference was seen in values of microalbuminuria in active inflammatory bowel disease patients receiving different salicylates. This study also measured serum amyloid-A as an indicator of the acute phase response in the same patients. Serum amyloid-A was significantly increased in active disease compared with inactive disease (151 (43) v 33 (7) or controls 11 (2) micrograms/ml, p < 0.05). In conclusion microalbuminuria is present in abnormal amounts in all patients with active inflammatory bowel disease, and values fall when the disease is quiescent. Microalbuminuria is probably a consequence of an acute phase response and provides a simple, rapid, and inexpensive test, which has the potential to monitor inflammatory bowel disease activity and response to treatment.

Acute-Phase Reaction↗

PubMed2026

Coordinated inflammatory macrophage and vascular smooth muscle cell remodeling signatures in human atherosclerosis: An integrative single-cell and bulk transcriptomic analysis.

Atherosclerotic plaque progression is shaped by coordinated inflammatory and remodeling programs involving immune cells and vascular wall cells. Inflammatory macrophage activation and vascular smooth muscle cell (VSMC) phenotypic remodeling are central features of human atherosclerosis, but their transcriptomic relationships during plaque progression remain incompletely characterized. This study integrated single-cell and bulk transcriptomic datasets to examine highly inflammatory macrophage states, VSMC remodeling-related transcriptional programs, and candidate ligand-receptor expression patterns in human atherosclerotic plaques. Human atherosclerotic plaque single-cell RNA sequencing data from GSE260657 and bulk transcriptomic data from GSE28829 were analyzed. After quality control, 7628 cells were retained for single-cell analysis. Major cell types were annotated using canonical markers, followed by reclustering of macrophages and VSMC-related cells. Functional module scoring, differential expression analysis, Gene Ontology biological process enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to characterize macrophage transcriptional states. Slingshot was applied to infer VSMC pseudotime ordering. CellChat and NicheNet were used to prioritize candidate ligand-receptor expression patterns and ligand-associated VSMC target gene programs. External bulk transcriptomic analysis was performed to examine whether single-cell-derived inflammatory and remodeling signatures were represented at the tissue-transcriptome level during plaque progression. Macrophage reclustering identified a highly inflammatory macrophage state characterized by prominent inflammatory activation, cytokine-response, and stress-response features. Genes upregulated in this population were enriched in pathways related to tumor necrosis factor (TNF) response, nuclear factor kappa B signaling, leukocyte activation, cytokine signaling, lipid and atherosclerosis, toll-like receptor signaling, and inflammasome-associated inflammation. VSMC reclustering revealed contractile VSMCs, PTHLH+ synthetic VSMCs, KRT7+ VSMC-like cells, interferon-responsive VSMCs, pericyte-like mural cells, and osteogenic/modulated VSMCs. Pseudotime analysis showed a broad contractile-to-osteogenic/modulated transcriptional continuum accompanied by increased expression of remodeling-associated genes and selected inflammatory or remodeling-associated receptor genes. CellChat and NicheNet analyses prioritized candidate ligand-receptor and ligand-associated target gene expression patterns involving SPP1-CD44, TNF-TNFRSF1A, IL1B-IL1R1/IL1RAP, MIF-ACKR3, PDGFB-PDGFRB, and FN1-SDC1/ITGB1. In GSE28829, inflammatory macrophage-, osteogenic/modulated VSMC-, candidate ligand-receptor expression-, SPP1-CD44 candidate axis-, and NicheNet-prioritized target program-related signatures were more prominent in advanced plaques and were positively correlated with each other. This integrative transcriptomic analysis identified a highly inflammatory macrophage state and a VSMC remodeling continuum in human atherosclerotic plaques. Candidate ligand-receptor and ligand-associated target gene expression patterns linked inflammatory macrophage activation with osteogenic/modulated VSMC remodeling at the computational level. External bulk data further showed coordinated enrichment of inflammatory and remodeling signatures in advanced plaques. These findings provide a descriptive and hypothesis-generating transcriptomic framework for understanding inflammatory macrophage activation and VSMC remodeling in human atherosclerosis.

atherosclerosis↗

PubMed2004

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity.

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.

Adult↗

PubMed2001

Anaplastic lymphoma kinase expression in inflammatory pseudotumors.

Anaplastic lymphoma kinase (ALK), a hallmark of anaplastic large cell lymphoma, has recently been implicated in the genesis of some inflammatory pseudotumors (inflammatory myofibroblastic tumors) in children and young adults. The aim of this study was to determine the frequency of its expression among inflammatory pseudotumors, and to characterize the clinicopathologic features of the positive cases. Sixty-one cases of inflammatory pseudotumors were retrieved from the surgical pathology archives and consultation files. Paraffin sections were immunostained with the antibody ALK1. The patients ranged in age from 0.5 to 79 years (median age, 50 years), with 10 patients (16.4%) younger than 20 years. Five cases (8.2%) were ALK+, including two of six urogenital inflammatory myofibroblastic tumors, none of eight pulmonary inflammatory pseudotumors, three (one adrenal, one small bowel, one liver) of 31 extrapulmonary inflammatory pseudotumors, none of nine hepatic/splenic inflammatory pseudotumors expressing follicular dendritic cell markers and harboring Epstein-Barr virus, and none of seven inflammatory pseudotumors of the lymph node. When only those patients 40 years or younger were considered, the ALK positivity rate became 21.7% (five of 23). All five ALK+ cases occurred in young patients aged 0.5 to 37 years, who were alive and well at 3.5 to 17 years. The tumors exhibited a spectrum of histologic features typical of inflammatory pseudotumors/myofibroblastic tumors, but there was at least focal nuclear atypia. Immunostaining for ALK produced fibrillary or granular cytoplasmic staining in the neoplastic cells, sometimes with cell membrane accentuation. This study confirms that ALK is implicated in a proportion of inflammatory pseudotumors, and is generally associated with a favorable outcome. The results also support the heterogeneity of inflammatory pseudotumors, with the follicular dendritic cell/Epstein-Barr virus-positive cases and those occurring in lymph nodes representing different biologic entities.

Adolescent↗

PubMed2000

Perturbations of arginine vasopressin secretion during inflammatory stress. Pathophysiologic implications.

Pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is pro-inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti-inflammatory and immunosuppressive effects of CS, is pro-inflammatory. Lewis rats develop a variety of induced-autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic-pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro-inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL-2 requirement for gamma IFN production by T cells via V1a receptors, and potentiates primary antibody responses, is also pro-inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease-resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague-Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL-6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis.

Animals↗

PubMed2005

Inflammatory processes in muscle injury and repair.

Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.

Animals↗

PubMed2002

Anti-inflammatory effects of IL-4 and IL-10 on human polymorphonuclear leukocytes.

Inflammatory responses are strictly regulated by coordination of pro-inflammatory and anti-inflammatory mediators. Interleukin-4 (IL-4) and interleukin-10 (IL-10) have typically the biologic anti-inflammatory effects on monocytes, but uncertain effects on polymorphonuclear leukocytes (PMNs). The PMNs are the first line of cellular response for host defense during acute inflammation. To modify hyper-inflammatory reaction with biologic anti-inflammatory mediators, we have determined the biologic anti-inflammatory activities of IL-4 and IL-10 on human PMNs. Human PMNs were pretreated with IL-4 or IL-10 and then stimulated with formyl methionyl leucyl phenylalanine (fMLP) for times indicated. The level of H2O2, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were determined in the each cell free supernatants. fMLP plays the role of a typical pro-inflammatory agent and, at least in determined conditions, down-regulated TNF release. IL-4 acts as an anti-inflammatory mediator but IL-10 did not show its anti-inflammatory activities on fMLP-stimulated human PMNs. IL-4 and IL-10 have different anti-inflammatory mechanisms. Perhaps, IL-10 needs co-factors to act as an anti-inflammatory mediator.

Cells, Cultured↗

PubMedDate not supplied

Thrombopoietin serum levels in patients with inflammatory bowel disease with and without previous thromboembolic events.

BACKGROUND/AIMS: Patients affected by inflammatory bowel disease frequently suffer from thromboembolic complications and mesenteric microvascular occlusion could be involved in the pathogenesis of inflammatory bowel disease. Increased platelet counts and abnormal platelet function seem to play a crucial role in determining the hypercoagulable state observed in inflammatory bowel disease. Thrombopoietin is considered the primary regulator of thrombopoiesis and recent studies have investigated the role of thrombopoietin in inflammatory bowel disease. However, the available data are not conclusive. The aim of this study was to assess thrombopoietin serum levels in inflammatory bowel disease patients according to platelet counts, disease activity and previous thrombotic events. METHODOLOGY: Seventy-one patients with inflammatory bowel disease [41 with ulcerative colitis and 30 with Crohn's disease] and 30 healthy controls were investigated. Eight (11%) inflammatory bowel disease patients had suffered previous thromboembolic complications, none had active thrombosis. Thrombopoietin serum levels were measured by ELISA. RESULTS: Mean thrombopoietin levels were significantly increased in inflammatory bowel disease patients with active disease compared to both healthy controls and patients with inactive disease. Platelet counts were significantly higher only in patients with active disease with respect to healthy subjects. No correlation was found between thrombopoietin levels and platelet counts in either controls or inflammatory bowel disease patients. No differences were found either in thrombopoietin levels or in platelet counts comparing inflammatory bowel disease patients with and without thromboembolic complications. CONCLUSIONS: Our data show elevated thrombopoietin levels in active inflammatory bowel disease. However, no correlation was found between platelet counts and thrombopoietin levels, supporting the hypothesis that other circulating factors than thrombopoietin interact in determining reactive thrombocytosis. Furthermore, thrombopoietin levels did not differ in inflammatory bowel disease patients with or without previous thromboembolic events. This finding could be probably explained by the lack of patients with active thrombosis at the moment of inclusion in the study.

Adult↗

PubMed2006

Importance of lipids in the nutritional treatment of inflammatory diseases.

Over the last decades, scientific advances in the knowledge of anti-inflammatory properties of lipids have lead to the development of new formulas for enteral and parenteral nutrition. These products have been utilised as a treatment for a variety of inflammatory diseases. In this review we expose the effects of lipids used in enteral nutriton on different inflammatory pathologies such as inflammatory bowel disease, atherosclerosis, lung fibrosis, rheumatoid arthritis, and others. During inflammatory diseases, eicosanoids are produced from polyunsaturated fatty acids present in cellular membranes. Inflammatory activity of these molecules depends on the nature of their precursors: when arachidonic acid (n-6) is present, pro-inflammatory molecules are released, whereas eicosapentaenoic acid (n-3)-derived eicosanoids are weakly inflammatory. In this way, fish oils, rich in n-3 polyunsaturated fatty acids, increase the content of eicosapentaenoic-eicosanoids and decrease arachidonic acid in immune and endothelial cells leading to a lower inflammatory activity. Likewise, oleic acid exhibits anti-inflammatory effects by preventing the release of particular chemotactic molecules. In summary, enteral diets supplemented with n-3 polyunsaturated fatty acids and oleic acid benefits the treatment of patients with inflammatory pathologies, leading to better outcomes, and decreasing the doses of anti-inflammatory drugs, which exhibit important secondary effects.

Cardiovascular Diseases↗

PubMed1993

Atypical pelvic inflammatory disease: can we identify clinical predictors?

OBJECTIVE: We used data from a large multicenter case-control study of tubal infertility to analyze further the relationship among demographic variables, behavioral measures, history of previous sexually transmitted diseases, and past contraceptive practices, for women with and without a history of pelvic inflammatory disease. STUDY DESIGN: We identified 283 white women with tubal infertility who requested care at seven participating institutions. Of these women, 238 (84%) did not have a history of pelvic inflammatory disease ("atypical pelvic inflammatory disease") whereas 45 reported a history of pelvic inflammatory disease ("overt pelvic inflammatory disease"). We compared these groups with 1629 white women without a history of either infertility or pelvic inflammatory disease who were delivered of their first live-born child at the same institutions as the infertile cases. RESULTS: Women with atypical pelvic inflammatory disease were demographically more like fertile control subjects and had behavioral characteristics midway between those of the overt pelvic inflammatory disease group and the fertile group. Both oral contraceptive and diaphragm use protected against tubal infertility for women with either atypical or overt pelvic inflammatory disease. Atypical pelvic inflammatory disease was related to a history of Trichomonas infection but not to a reported history of gonorrhea, genital herpes, or other vaginitis. CONCLUSION: Atypical pelvic inflammatory disease is probably more common than its symptomatic counterpart. Whereas this condition is associated with some characteristics of a sexually transmitted infection, clinical predictors remain elusive.

Adult↗

PubMed2005

MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits.

Excessive inflammation is becoming accepted as a critical factor in many human diseases, including inflammatory and autoimmune disorders, neurodegenerative conditions, infection, cardiovascular diseases, and cancer. Cerebral ischemia and neurodegenerative diseases are accompanied by a marked inflammatory reaction that is initiated by expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. This review discusses recent advances regarding the detrimental effects of inflammation, the regulation of inflammatory signalling pathways in various diseases, and the potential molecular targets for anti-inflammatory therapy. Mitogen-activated protein kinases (MAPKs) are a family of serine/threonine protein kinases that mediate fundamental biological processes and cellular responses to external stress signals. Increased activity of MAPK, in particular p38 MAPK, and their involvement in the regulation of the synthesis of inflammation mediators at the level of transcription and translation, make them potential targets for anti-inflammatory therapeutics. Inhibitors targeting p38 MAPK and JNK pathways have been developed, and preclinical data suggest that they exhibit anti-inflammatory activity. This review discusses how these novel drugs modulate the activity of the p38 MAPK and JNK signalling cascades, and exhibit anti-inflammatory effects in preclinical disease models, primarily through the inhibition of the expression of inflammatory mediators. Use of MAPK inhibitors emerges as an attractive strategy because they are capable of reducing both the synthesis of pro-inflammatory cytokines and their signalling. Moreover, many of these drugs are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disease.

Anti-Inflammatory Agents↗

PubMed2005

Enhancing anti-inflammatory cytokine IL-10 may be beneficial for acute coronary syndrome.

Inflammation is one of the basic biological responses against vascular injury. It has been demonstrated, however, that inflammation is an important pathogenic feature in atherosclerotic lesions. Previous data showed that pro-inflammatory cytokines played an important role in acute coronary events. A complex intravascular inflammatory response is also an integral component of atherosclerotic plaque dynamic instability, and the imbalance between anti-inflammatory mechanisms and pro-inflammatory factors, in favor of the pro-inflammatory factors, will result in rupture of atherosclerotic plaque. Interluekine-10 (IL-10), which is produced by various inflammatory cells, especially macrophages, has multifaceted anti-inflammatory properties, including inhibition of the prototypic pro-inflammatory transcription factor nuclear factor-kappaB, leading to suppressed cytokine production, inhibition of matrix degrading metalloproteinase production, reduction of tissue factor expression, inhibition of apoptosis of macrophages and monocytes after infection, and promotion of the phenotypic switch of lymphocytes into the Th2 phenotype. All these inflammatory mechanisms have been shown to play a pivotal role for atheroslerotic lesion development and progression, indicating a potential regulatory role of IL-10. More recent data showed that decreased plasma concentration of anti-inflammatory cytokine IL-10 was associated with acute coronary syndrome. Therefore, we hypotheses that enhancing anti-inflammatory cytokine IL-10 may be a promising approach for the therapy of acute coronary diseases.

Acute Disease↗

PubMed1998

Severity of pelvic inflammatory disease as a predictor of the probability of live birth.

OBJECTIVE: Our aim was to study the association between severity of pelvic inflammatory disease at laparoscopy and the probability of achieving a live birth, while accounting for subsequent episodes of pelvic inflammatory disease. STUDY DESIGN: Beginning in 1960 a cohort of 1288 women in Lund, Sweden, who had clinical symptoms of acute pelvic inflammatory disease and who desired pregnancy was followed for up to 24 years. All participants underwent laparoscopy and were categorized by degree of salpingitis: mild (n = 371), moderate (n = 580), or severe (n = 337) pelvic inflammatory disease. Cumulative live birth rates, obtained by life-table analysis, and proportional hazards ratios were compared among women by severity of pelvic inflammatory disease, while accounting for subsequent episodes. RESULTS: The cumulative proportion of women achieving a live birth after 12 years was 90% for women with mild, 82% for women with moderate, and 57% for women with severe pelvic inflammatory disease. The occurrence of subsequent episodes in women with mild pelvic inflammatory disease did not diminish their long-term probability of live birth, whereas it significantly lowered the probability of live birth in women with severe pelvic inflammatory disease. Women with severe disease and subsequent episodes were eight times more likely to fail to achieve live birth compared with women with a single pelvic inflammatory disease episode with mild disease (relative risk 8.1; 95% confidence interval 3.0 to 22.2). CONCLUSIONS: Increasing severity of pelvic inflammatory disease correlates with a lower long-term probability of live birth. Subsequent episodes have a greater impact on women with severe pelvic inflammatory disease at the index episode compared with those with milder disease.

Adult↗

PubMed1999

Clinical applications of technetium Tc 99m hexamethyl propylene amine oxime leukocyte scan in children with inflammatory bowel disease.

BACKGROUND: Labeled leukocyte imaging is a helpful diagnostic tool in the detection of inflammation and sepsis. The technetium Tc 99m hexamethyl propylene amine oxime (99mTc HMPAO)-labeled leukocyte scan has been found to be more sensitive than the Indium-111 labeled leukocyte scan in detecting inflammatory bowel disease, with reported sensitivities of 95% to 100%. Experience with the 99mTc HMPAO-labeled leukocyte scan was examined and its clinical applications evaluated in the immediate treatment of patients with inflammatory bowel disease. METHODS: A retrospective chart review was undertaken that included pediatric patients who underwent 99mTc HMPAO-labeled leukocyte scan at the James Whitcomb Riley Hospital for Children. The disease activity of patients with inflammatory bowel disease was assessed. The leukocyte scan was performed according to the manufacturer's specifications, and images were obtained 30 minutes and 2 hours after administration of the radiopharmaceutical. RESULTS: During the period of July 1996 through November 1997, 41 scans were performed in 35 patients. Twenty-nine patients had histologically proven inflammatory bowel disease: 24 with Crohn's disease, 4 with ulcerative colitis, and 1 with indeterminate colitis. Active inflammatory bowel disease was suspected in 24 patients when the leukocyte scan was performed. Twenty of the 24 patients (83% sensitivity) had abnormal findings in leukocyte scans that prompted more aggressive management in 15 (75%). Six of the 15 who were receiving maximum medical therapy underwent surgical resection of severely affected bowel segments, and medical treatment was intensified in the other 9. The remaining 5 patients were receiving optimal medical therapy, instituted at their recent visit, and did not require further medication adjustments. Four of the 24 patients with active inflammatory bowel disease had normal leukocyte scans (17% false-negative rate), 3 of whom were receiving corticosteroid therapy at the time the scans were performed. All of the 11 patients in whom inflammatory bowel disease was in remission and 6 patients who did not have inflammatory bowel disease had normal findings in leukocyte scans (100% specificity). CONCLUSIONS: Although a tissue diagnosis is still recommended, obtained during upper and lower gastrointestinal endoscopic examinations, and contrast radiography of the small bowel for the initial work-up of patients with suspected inflammatory bowel disease, the 99mTc HMPAO-labeled leukocyte scan is a safe and useful diagnostic adjunct for subsequent evaluation of patients known to have inflammatory bowel disease. The results of 99mTc HMPAO-labeled leukocyte scans directly influenced treatment of 75% of the study patients with active inflammatory bowel disease, which included the decision to refer patients for surgical intervention.

Adolescent↗

PubMed1995

Inflammatory Bowel Disease Questionnaire: cross-cultural adaptation and further validation.

OBJECTIVES: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific quality of life instrument. We translated and adapted the questionnaire and tested its reliability and (cross-cultural) validity. METHODS: We surveyed 271 patients with inflammatory bowel disease. The inflammatory Bowel Disease Questionnaire and its dimensional scores (bowel, systemic, social and emotional) were correlated with disease activity, health care use, medication and three other indices of quality of life. RESULTS: The reliability coefficient of the Inflammatory Bowel Disease Questionnaire was high (0.93). Patients with higher disease activity had significantly lower quality of life on all Inflammatory Bowel Disease Questionnaire dimensions (P < 0.001). Inflammatory Bowel Disease Questionnaire scores were significantly correlated with health care use (P < 0.01) but not with medication. Almost all Inflammatory Bowel Disease Questionnaire dimensions correlated highly (0.43-0.79, P < 0.001) with the corresponding scales of the standard quality of life indices, except for the bowel dimension. Modified Dutch Inflammatory Bowel Disease Questionnaire scores were consistent with Canadian Inflammatory Bowel Disease Questionnaire norms. CONCLUSIONS: These results support the Inflammatory Bowel Disease Questionnaire as a reliable and valid measure of the quality of life of inflammatory bowel disease patients in multicultural research settings.

Adaptation, Psychological↗

PubMed2006

Oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis : case reports and review of the literature.

Inflammatory flare-up reactions of some dermatomycoses, particularly those caused by zoophilic fungi, are typical and potentially severe adverse effects following the intake of some oral antifungals. However, this condition has not previously been reported with the most frequently used antifungals in dermatology, namely fluconazole, itraconazole, and terbinafine. In this report, we describe five patients, observed over a 10-year period, who presented with inflammatory exacerbations following oral antifungal therapy for dermatomycoses. We also review the literature on inflammatory reactions exacerbated by oral antifungal agents. Details of the patients' age, sex, occupation, and atopic background; the site of the lesion, its clinical and histologic features, and any systemic signs; the identity of the fungal pathogen; the antifungal agent taken by the patient; the time between drug intake and occurrence of the flare-up; the approach to management; and the outcome were documented for each patient. A PubMed literature search was also conducted, focusing on inflammatory exacerbations induced by griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. The patients were four farmers and one veterinarian (all male). All primary lesions were inflammatory dermatophytoses, including one kerion. Inflammatory exacerbation of the skin lesions started 12-24 hours after the intake of oral antifungals. Mild systemic changes, including slight fever and malaise, occurred in two cases. Itraconazole 400 mg/day was implicated as the causative agent in four cases and terbinafine 250 mg/day in one case. Mycologic cultures grew Trichophytonverrucosum in four cases. Antifungal treatment was discontinued in all patients. Oral and topical corticosteroids were administered to the two patients with systemic changes; the other three patients were treated with topical corticosteroids only. Two days after the onset of corticosteroids, lower doses of itraconazole (100 mg/day) and terbinafine (125 mg/day) were reintroduced. All lesions healed after 4-5 weeks. The PubMed search did not identify any articles that described inflammatory exacerbations of dermatomycoses induced by oral antifungals. Inflammatory flare-up of dermatomycoses is a rare but potentially severe cutaneous complication of oral antifungal use. Occupational contact with animals, inflammatory dermatomycoses, and zoophilic fungi represent common features in these patients. Although evidence-based data are not available, clinical experience shows that, in addition to antifungal therapy, topical and/or systemic corticosteroids are helpful to reduce the inflammatory reactions. The cases described in this article represent the first published report of oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis in patients taking itraconazole or terbinafine.

Administration, Oral↗

PubMed2002

From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer's disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia.

Epidemiological evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) may protect against Alzheimer's disease (AD). However, therapeutic studies with NSAIDs, including cyclooxygenase (COX) inhibitors and steroids have not supported such epidemiological evidence. The apparent inconsistency may be due to the fact that the epidemiological evidence is based on studies examining AD before clinical manifestations are apparent, while therapeutic studies have been carried out on people with illnesses severe enough to exceed the clinical detection threshold. Thus, it is conceivable that therapeutic strategies administered during early AD dementia or moderate dementia may not be optimally effective. Alternatively, the influence of inflammatory activity in the brain for cases at high risk to develop AD, e.g., mild cognitive impairment (MCI) cases, as a potential target of anti-inflammatory drugs in clinical studies maybe more suitable to be studied. The primary action of NSAIDs is inhibition of the COX enzymes. COX enzymes exist in an inducible form COX-2, that has been found to be elevated in the AD brain, and a constitutive form COX-1. Both COX-1 and COX-2 are known to be involved in numerous inflammatory activities as well as normal neuronal functions. In vitro, it has been demonstrated that non-selective inhibitors of COX can preferentially decrease the levels of the highly amyloidogenic amyloid-beta (Abeta)(1-42)peptide. Recent studies testing non-selective NSAIDs in murine models of AD neuropathology indicated that the frequency of Abeta plaque deposits in the brains of these animals can be significantly reduced by treatment with the non-selective COX inhibitor ibuprofen. These studies and epidemiological data strongly support a therapeutic potential for NSAIDs in the treatment of AD. Upon this premise, industry and academia are devoting a tremendous amount of resources to the testing of anti-inflammatory drugs for the treatment of AD. However, given the large number of candidate anti-inflammatory drugs and their widely divergent activities, it is essential to optimize drug selection and study design. A better understanding of the influence of inflammatory activity in AD, and identification of the specific mechanisms which play an early role in the disease's progression will greatly improve the likelihood of success in efforts to find an effective anti-inflammatory treatment strategy. We would like to discuss recent developments reinforcing anti-inflammatory drugs as therapeutic in the treatment of AD amyloidosis, and the relevance of understanding the role of COX and other inflammatory mediators in AD neuropathology and the clinical progression of AD dementia. These discussions may provide important criterion for the design of clinical trials of anti-inflammatory drugs in AD.

Alzheimer Disease↗

PubMed2003

The use of IL-6 induction as a human biomarker for inflammatory agents in water.

A rapid whole blood culture (WBC) assay system was developed to monitor the inflammatory potential of water samples collected in the Manguang Municipal area, South Africa. Several systems associated with the Modder River catchment area were investigated in this preliminary study to find out whether there were potential problems in this catchment area. Three focus areas were investigated: (a) the impact of the Klein Modder River, which passes through a densely populated residential area, on the inflammatory activity of the Modder River; (b) the efficiency of the treatment plants in eliminating inflammatory activity; and (c) the efficiency of chlorination of treated water in eliminating inflammatory activity that was not eliminated by the treatment system. Water contaminated with inflammatory substances induced the pro-inflammatory hormone interleukin 6 (IL-6). All water samples collected from the Modder River induced IL-6 secretion, and the quantity of IL-6 secreted was dependent on the concentration and origin of the sample. The lowest IL-6 inducing activity for river water was obtained for samples collected near the origin of the river (Rustfontein). Samples at subsequent points downstream from confluence with the Klein Modder River showed a major increase in IL-6 inducing activity. The two treatment plants along the Modder River also received water of different inflammatory activity. Both treatment plants eliminated some of the inflammatory activity during processing, however inflammatory residues remained after processing which might have been potentially harmful for infants and people with suppressed immune systems. Chlorination eliminated most of the inflammatory activity, indicating that chlorination of water was a necessary process in ensuring water of low inflammatory content.

Anti-Inflammatory Agents↗