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Nitrogen supplementation of corn silages. 2. Assessing rumen function using fatty acid profiles of bovine milk.

The effects of N supplementation strategies on milk fatty acid profiles of dairy cows and their use as a noninvasive technique to diagnose rumen function, and to guide protein feeding decisions on-farm were evaluated in three experiments. Each experiment was designed according to three 3 x 3 Latin squares with 9 Holstein cows receiving total mixed rations based on corn silage. Experiment 1 was designed to study effects of diets with different ratios of effective rumen-degradable protein (ERDP; g) to fermentable metabolizable energy (FME; j) providing, respectively, a large deficiency, a slight deficiency, and a slight excess in relation to the target level of 11 g of ERDP/MJ FME for lactating cows. Experiment 2 evaluated effects of different proportions of quickly and slowly rumen-degradable protein achieved by replacing soybean meal with urea in the concentrates (0, 0.5, and 1% urea for U0, U5, and U10, respectively). Experiment 3 investigated effects of synchronizing the availability of FME and ERDP in rumen by offering the protein-rich concentrate once or twice per day before the meal (corn silage, ryegrass hay, and energy-rich concentrate), or included in the total mixed ration. Milk fatty acid profiles were significantly affected by dietary N and carbohydrate supply. Principal component factor analysis provided a reasonable description of the data, clearly discriminating between fatty acids that are synthesized by different metabolic pathways. Several sources/pathways were distinguished: de novo synthesis in the mammary gland (short- and medium-chain fatty acids), delta9-desaturase activity (monoenoic fatty acids), direct absorption from the blood stream (long-chain fatty acids), and de novo synthesis by the rumen microbial populations (odd-chain fatty acids). Discriminant canonical analysis showed that milk odd-chain fatty acids had a higher ability to discriminate between diets than even-chain fatty acids. The anteiso C15:0 increased in line with increasing sugar supply, and C17:0 appears to be a marker of protein deficiency. Additionally, iso C17:0 and anteiso C17:0 were associated with the NDF and CP contents of diets. The results suggests that milk odd-chain fatty acids have the potential to be used as a noninvasive technique to assess rumen function in terms of microbial populations, substrates and interactions.

Animals↗

Improvement of cardiac performance and cardiovascular risk factors in children with GH deficiency after two years of GH replacement therapy: an observational, open, prospective, case-control study.

CONTEXT: GH deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. OBJECTIVE: The aim of this study was to evaluate the effect of GHD and GH replacement therapy on cardiac performance, lipid profile, and insulin resistance in children. DESIGN: This was a 2-yr case-control prospective study. PATIENTS: Thirty children with GHD aged 9.3 +/- 0.5 yr and 30 healthy matched controls were studied. INTERVENTION: Children were studied before and after 1 and 2 yr of GH replacement (GHD children) or no treatment (controls). MAIN OUTCOME MEASURES: Lipid profile, serum insulin levels, homeostasis model of assessment (HOMA) index, and left ventricular (LV) mass and function by echocardiography were the main outcome measures. RESULTS: At study entry, the LV mass index was significantly lower in GHD children (50.2 +/- 1.7) than in controls (60.3 +/- 2.5 g/m(2); P < 0.002), whereas LV systolic and diastolic function, lipid profile, insulin levels, and HOMA index were similar. In GHD children LV mass index significantly increased (66.3 +/- 2.4 g/m(2); P < 0.0001) after 1 yr of GH replacement and remained stable thereafter. LV systolic and diastolic function did not change during treatment. After 2 yr of GH replacement, total cholesterol (P < 0.007) and the atherogenic index (P < 0.0001) significantly decreased, whereas fasting insulin levels (P < 0.001) and HOMA index (P < 0.0001) significantly increased compared with both pretreatment and control values. CONCLUSIONS: GHD in children is associated with a reduced cardiac size but with a normal cardiac function, lipid profile, and insulin sensitivity. Two years of GH replacement normalizes cardiac morphology, improves lipid profile, and slightly impairs insulin sensitivity.

Cardiovascular Diseases↗

Hepatic insulin gene therapy prevents deterioration of vascular function and improves adipocytokine profile in STZ-diabetic rats.

Hepatic insulin gene therapy (HIGT) ameliorates hyperglycemia in diabetic rodents, suggesting that similar approaches may eventually provide a means to improve treatment of diabetes mellitus. However, whether the metabolic and hormonal changes produced by HIGT benefit vascular function remains unclear. The impact of HIGT on endothelium-dependent vasodilation, nitrosyl-hemoglobin content (NO-Hb), and insulin sensitivity were studied using aortic ring preparations, electron spin resonance spectroscopy (ESR), homeostasis assessment of insulin resistance (HOMA-IR) calculations, and insulin tolerance testing (ITT). Data were correlated with selected hormone and adipocytokine concentrations. Rats made diabetic with streptozotocin were treated with subcutaneous insulin pellets dosed to sustain body weights and hyperglycemia or with HIGT; nondiabetic rats served as controls. Hyperglycemic rats demonstrated impaired endothelium-dependent vasodilation, reduced levels of NO-Hb, and diminished insulin, leptin, and adiponectin concentrations compared with controls. In contrast, HIGT treatment significantly reduced blood sugars and sustained both endothelium-mediated vasodilation and NO-Hb at control levels. HOMA-IR calculations and ITT indicated enhanced insulin sensitivity among HIGT-treated rats. HIGT partially restored suppressed leptin levels in hyperglycemic rats and increased adiponectin concentrations to supranormal levels, consistent with indicators of insulin sensitivity. Our findings indicate that the metabolic milieu produced by HIGT is sufficient to preserve vascular function in diabetic rodents. These data suggest that improved glycemia, induction of a beneficial adipocytokine profile, and enhanced insulin sensitivity combine to preserve endothelium-dependent vascular function in HIGT-treated diabetic rats. Consequently, HIGT may represent a novel and efficacious approach to reduce diabetes-associated vascular dysfunction.

Acetylcholine↗

Osteoscintimetry--a method of semiquantitative evaluation of skeletal scintigrams by use of profiles and a macro function for computer processing.

A computer macro-program was developed for standardized, semiquantitative measurement of radiotracer uptake. The method uses profiles of selectable length, width, and inclination according to the anatomical structures of the pathological and the corresponding healthy region. The ratio of the two curves is calculated automatically and shown as an 'uptake curve'. The essential use of osteoscintimetry is in the follow-up examination if small changes of regional uptake have to be identified. The profile-technique rather than the ROI-technique was selected, because the main benefit of the profile-technique is that the results of follow-up examinations are comparable to previous examinations with a standard deviation of +/-5%.

Adolescent↗

The ilio-marsupialis muscle in the dasyurid marsupial Sminthopsis douglasi: form, function and fibre-type profiles in females with and without suckling young.

The form, function and fibre-type profiles of the ilio-marsupialis muscles, branches of which insert on to the skin of the nipples and pouch, have been investigated in the small dasyurid marsupial Sminthopsis douglasi. Single fibres from the branches of muscles associated with unsuckled nipples in non-lactating females and with both unsuckled and suckled nipples at four stages during the 70-day suckling period were typed according to their sensitivity to the activators strontium (Sr(2+)) and calcium (Ca(2+)) into fast-twitch, slow-twitch and composite types. An unusual finding was the predominance of composite fibres in the resting state (unsuckled nipples). Changes in fibre-type composition were observed during the suckling period and these changes correlated with events in the development of the suckling young. Composite fibres declined during the suckling period and, at the stage when the young can no longer be accommodated in the pouch but must still be carried by the mother while she is foraging, an increase in fast-twitch fibres that are associated with dynamic muscular activity was seen. Later in the suckling period, when the mammary tissue is greatly enlarged but the mother does not carry the young while out feeding, there was an increase in the proportion of slow-twitch (fatigue-resistant) fibres. The high proportion of fast-twitch fibres present late in the suckling period may be associated with vibratory movements that result in the young relinquishing the nipples.

Animals↗

Effect of PLC on functional parameters and oxidative profile in type 2 diabetes-associated PAD.

OBJECTIVE: To investigate the effects of propionyl l-carnitine (PLC) on clinical and functional parameters, and markers of the overall oxidation state in patients with peripheral arterial disease (PAD) associated with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN AND SETTING: Randomised, double-blind, clinical trial, conducted in the Unit of Medical Angiology of the University of Catania. PATIENTS AND INTERVENTIONS: Seventy-four patients with NIDDM-associated PAD were treated with PLC (2 g/day) or placebo for 12 months. MAIN OUTCOME MEASURES: Ankle/brachial index (ABI) and the distance of pain-free walking were evaluated at baseline, 6 and 12 months. Malondialdehyde, 4-hydroxynonenal, oxidation time of low-density lipoproteins, and nitrite/nitrate ratio were measured as indices of the overall oxidation profiles at baseline and 12 months. RESULTS: In the PLC group, ABI progressively increased (0.78, 0.83, and 0.88 at 0, 6 and 12 months, respectively). The distance of pain-free walking also improved (366.4, 441.9 and 519.8 m, respectively). In the placebo group, these parameters were relatively unchanged. Significant improvements in all parameters of the oxidative profile were seen in the PLC-treated group, with only minor variations observed in the placebo group. CONCLUSIONS: These results suggest that adjunct therapy with PLC may be warranted in type 2 diabetes-associated PAD.

Aged↗

Genome-wide transcriptional profiles are consistent with functional specialization of the extraocular muscle layers.

PURPOSE: Compartmentalization of the extraocular muscles into well-defined orbital and global layers is highly conserved. Recently, the active pulley hypothesis correlated the anatomic properties of orbital-global muscle layers with layer-specific division of labor. Microarray technology was used to identify muscle-layer-specific transcriptional profiles and, thereby, extend understanding of the structure-function characteristics of extraocular muscle layers. METHODS: Laser capture microdissection was used to obtain muscle layer samples from monkey medial rectus muscles. RNA was linearly amplified and hybridized to human U133 series microarrays (Affymetrix, Santa Clara, CA), which have sufficient sequence homology for use in subhuman primates. Data was analyzed using Affymetrix and Robust Multichip Average (RMA) algorithms. Select transcripts were verified by quantitative PCR and in situ hybridization. RESULTS: A broad spectrum of transcriptional differences (> 181 transcripts) was identified between the two extraocular muscle layers. Patterned differences in the sarcomeric contractile machinery and cytoskeleton were suggestive of key layer differences in contraction speed. Differentially expressed transcript identities, however, extended well beyond those traditionally associated with muscle-fiber-group differences. CONCLUSIONS: Muscle layer transcriptional profiles correlated with the different loads and usage patterns of extraocular muscle layers, as proposed in the active pulley hypothesis. The magnitude and breadth of orbital-global layer expression differences strongly suggests that oculomotor control systems may drive two distinct motor output pathways, each comprising separate motoneurons and muscle fibers, with one output path adapted to determining pulley position and the other to movement of the eye.

Animals↗

An evaluation of different growth functions for describing the profile of live weight with time (age) in meat and egg strains of chicken.

A total of 86 profiles from meat and egg strains of chickens (male and female) were used in this study. Different flexible growth functions were evaluated with regard to their ability to describe the relationship between live weight and age and were compared with the Gompertz and logistic equations, which have a fixed point of inflection. Six growth functions were used: Gompertz, logistic, Lopez, Richards, France, and von Bertalanffy. A comparative analysis was carried out based on model behavior and statistical performance. The results of this study confirmed the initial concern about the limitation of a fixed point of inflection, such as in the Gompertz equation. Therefore, consideration of flexible growth functions as an alternatives to the simpler equations (with a fixed point of inflection) for describing the relationship between live weight and age are recommended for the following reasons: they are easy to fit, they very often give a closer fit to data points because of their flexibility and therefore a smaller RSS value, than the simpler models, and they encompasses simpler models for the addition of an extra parameter, which is especially important when the behavior of a particular data set is not defined previously.

Aging↗

Suberosis and bird fancier's disease: a comparative study of radiological, functional and bronchoalveolar lavage profiles.

Hypersensitivity Pneumonitis (HP) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles have been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of HP seen in our practice: Suberosis (an HP related to moldy cork dust exposure) and bird fancier's disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8 +/- 11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3 +/- 11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of HP had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 10(5) ml-l cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-l cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in bird fancier's disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p < 0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are HP with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Adult↗

Systems-wide chicken DNA microarrays, gene expression profiling, and discovery of functional genes.

The goal of our current consortium project is to launch a new era--functional genomics of poultry--by providing genomic resources [expressed sequence tags (EST) and DNA microarrays] and by examining global gene expression in target tissues of chickens. DNA microarray analysis has been a fruitful strategy for the identification of functional genes in several model organisms (i.e., human, rodents, fruit fly, etc.). We have constructed and normalized five tissue-specific or multiple-tissue chicken cDNA libraries [liver, fat, breast, and leg muscle/epiphyseal growth plate, pituitary/hypothalamus/pineal, and reproductive tract (oviduct/ovary/testes)] for high-throughput DNA sequencing of EST. DNA sequence clustering was used to build contigs of overlapping sequence and to identify unique, non-redundant EST clones (unigenes), which permitted printing of systems-wide chicken DNA microarrays. One of the most promising genetic resources for gene exploration and functional gene mapping is provided by two sets of experimental lines of broiler-type chickens developed at INRA, France, by divergent selection for extremes in growth traits (fast-growing versus slow-growing; fatness versus leanness at a similar growth rate). We are using DNA microarrays for global gene expression profiling to identify candidate genes and to map growth, metabolic, and regulatory pathways that control important production traits. Candidate genes will be used for functional gene mapping and QTL analysis of F2 progeny from intercrosses made between divergent genetic lines (fat x lean lines; fast-growing x slow-growing lines). Using our first chicken liver microarray, we have already identified several interesting differentially expressed genes in commercial broilers and in divergently selected broiler lines. Many of these candidate genes are involved in the lipogenic pathway and are controlled in part by the thyrotropic axis. Thus, genome-wide transcriptional profiling is a powerful tool used to visualize the cascade of genetic circuits that govern complex biological responses. Global gene expression profiling and QTL scans should enable us to functionally map the genetic pathways that control growth, development, and metabolism of chickens. This emerging technology will have broad applications for poultry breeding programs (i.e., use of molecular markers) and for future production systems (i.e., the health and welfare of birds and the quality of poultry products).

Animal Husbandry↗

Molecular profiling of antipsychotic drug function: convergent mechanisms in the pathology and treatment of psychiatric disorders.

Despite great progress in antipsychotic drug research, the molecular mechanisms by which these drugs work have remained elusive. High-throughput gene profiling methods have advanced this field by allowing the simultaneous investigation of hundreds to thousands of genes. However, different methodologies, choice of brain region, and drugs studied have made comparisons across different studies difficult. Because of the complexity of gene expression changes caused by drugs, teasing out the most relevant expression differences is a challenging task. One approach is to focus on gene expression changes that converge on the same systems that were previously deemed important to the pathology of psychiatric disorders. From the microarray studies performed on human postmortem brain samples from schizophrenics, the systems most implicated to be dysfunctional are synaptic machinery, oligodendrocyte/myelin function, and mitochondrial/ubiquitin metabolism. Drugs may act directly or indirectly to compensate for underlying pathological deficits in schizophrenia or via other mechanisms that converge on these pathways. Side effects, consisting of motor and metabolic dysfunction (which occur with typical and atypical drugs, respectively), also may be mediated by gene expression changes that have been reported in these studies. This article surveys both the convergent antipsychotic mechanisms and the genes that may be responsible for other effects elicited by antipsychotic drugs.

Animals↗

Integrated functional, metabolomic, and biotransformation profiling of mycotoxin hepatotoxicity in 2D and 3D human hepatic models.

Mycotoxins pose a major risk to food safety and human health, yet their hepatotoxic mechanisms remain incompletely characterized due to limitations in conventional in vitro models. In this study, we systematically compared mycotoxin-induced hepatotoxicity and metabolomic profiling across two human hepatic models cultured under 2D monolayer and 3D spheroid conditions. The various mycotoxins (Aflatoxin B1, Citrinin, Deoxynivalenol, Ochratoxin A, Patulin, and Zearalenone) exhibit distinct metabolic signatures, thereby serving as an appropriate panel for comprehensively evaluating diverse hepatotoxic mechanisms. Mycotoxin exposure induced concentration-dependent hepatotoxicity accompanied by functional impairment and structural disruption in hepatic models. Metabolomic profiling revealed distinctive regulatory patterns between 2D and 3D hepatic models, with 3D spheroids showing consistent down-regulation across multiple intracellular metabolic pathways and altered extracellular metabolite release, whereas 2D monolayers predominantly exhibited global metabolic activation. In silico-assisted MS/MS analysis further demonstrated that Phase I biotransformation was largely conserved across models, whereas Phase II conjugation reactions were more frequently detected and exhibited greater model specificity in 3D spheroids. Overall, these findings indicate that 3D hepatic spheroids capture more integrated and coordinated hepatotoxic and metabolic responses to mycotoxins compared with 2D monolayer systems. These distinctive regulatory dynamics support their value as a physiologically relevant platform for toxicity assessment and mechanistic investigation.

3D hepatic spheroids↗

[Suberosis and bird fancier's disease: comparative study of radiological, functional and bronchoalveolar characteristics profile].

Extrinsic Allergic Alveolitis (EAA) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles has been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of EAA seen in our practice: Suberosis and Bird Fancier's Disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8+/-11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3+/-11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of EAA had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 105 ml-1 cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-1 cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in Bird Fancier's Disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p <0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are EAA with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Adult↗

[Mirror phenomena in patients with different autoimmune disorders].

The aim of the article was to study functional asymmetry between hemispheres and to find an ability to mirror phenomena in 25 patients with systemic lupus erythematosus (SLE) and 12 patients with multiple sclerosis. Patients with SLE had the following individual profiles of functional asymmetry: right, mainly right, mixed and mainly left. Nobody of them had either symmetric or left profiles. An ability to mirror phenomena (mirror drawing and mirror writing) has been found in 56% of SLE patients with different individual profiles of functional asymmetry. These patients significantly differed from the control group and patients with multiple sclerosis.

Adult↗

Cerium dioxide nanoparticle exposure attenuates mobility-linked antibiotic resistome signatures across the soil-lettuce continuum.

Antibiotic resistance genes (ARGs) are contaminants of emerging concern in agricultural microbiomes. Their association with mobile genetic elements (MGEs) can enhance dissemination across soil-plant interfaces, creating potential environmental and food-chain exposure risks. However, how engineered nanoparticles modulate relative ARG abundance and mobility-linked resistome features in plant-associated microbiomes remains poorly understood. Here, we examined the effects of graded, experimentally elevated cerium dioxide nanoparticle (CeO2 NP) loadings in a soil-lettuce system by integrating compartment-resolved metagenomics, ARG-MGE co-occurrence analysis, putative host-reservoir profiling, transcriptomics, and functional assays. Metagenomic profiling identified 16 ARG types and 125 subtypes and revealed niche-dependent microbiome restructuring under CeO2 NP exposure. Rhizosphere relative ARG abundance showed a negative dose-associated trend, although overall inter-group differences were not significant, whereas leaf endophytes showed a weaker response. Relative MGE abundance decreased significantly in both compartments, and lower assembly-level ARG-MGE co-occurrence reflected fewer ARGs detected in MGE-associated genomic contexts, whereas fewer multi-ARG contigs suggested reduced ARG clustering and potential co-selection. Putative host-reservoir analysis associated key efflux determinants with bacterial families whose relative representation declined following CeO2 NP exposure. Transcriptomic profiling of representative putative ARG hosts revealed host-specific responses, including downregulation of genes involved in central metabolism and Sec-dependent trafficking. Complementary host assays showed reduced apparent envelope permeability and lower recovery of tetracycline-resistant recipient-identity colonies in the plasmid-associated host system. Together, under the tested elevated-loading conditions, CeO2 NP exposure was associated with lower relative ARG signals and weaker mobility-linked resistome features across the soil-lettuce continuum, providing mechanistic insight into nanoparticle-resistome interactions in soil-plant systems.

ARG dissemination↗

Analogues of vaccinia virus DNA topoisomerase I modified at the active site tyrosine.

The mechanism of type IB topoisomerase-mediated DNA relaxation was studied by modification of vaccinia topoisomerase I at the active site tyrosine (position 274) with several tyrosine analogues. These analogues had varied steric, electronic, and stereochemical features to permit assessment of those structural elements required to support topoisomerase function. Eleven tyrosine analogues were successfully incorporated into the active site of vaccinia topoisomerase I. It was found that only tyrosine analogues having the phenolic -OH group in the normal position relative to the protein backbone were active. Modifications that replaced the nucleophilic tyrosine OH (pKa approximately 10.0) group with NH2 (pKa 4.6), SH (pKa approximately 7.0), or I groups or that changed the orientation of the nucleophilic OH group essentially eliminated topoisomerase I function. For the active analogues, the electronic effects and H-bonding characteristics of substituents in the meta-position of the aromatic ring may be important in modulating topoisomerase I function. The pH profile for the functional analogues revealed a small shift toward lower pH when compared with wild-type topoisomerase I.

Amino Acid Sequence↗

Profile changes in modified functional regulator therapy.

Comparison of lateral cephalometric radiographs of treatment and control groups finds the changes achieved with a modified functional regulator are limited to improvement in dental and lip relations. No effects are found on mandibular growth or position in relation to the profile.

Activator Appliances↗

Pulmonary and hematological alterations in idiopathic ulcerative colitis.

BACKGROUND: Patients with idiopathic ulcerative colitis (IUC) may suffer from one or more extraintestinal manifestations. We decided to prospectively study the prevalence of extraintestinal manifestations among patients with IUC, with special reference to pulmonary and hematological alterations. METHODS: Fifty-one consecutive patients with IUC attending the gastroenterology services of our tertiary-care referral center were evaluated prospectively. A detailed clinical evaluation of the musculoskeletal system, eye and skin, X-ray examination of the sacroiliac joints and chest, liver function tests, coagulation profile, hemogram, pulmonary function tests (PFT) and diffusion capacity for carbon monoxide (DLCO) were done in all patients. ERCP, liver biopsy and high-resolution computerized tomography (HRCT) of the chest were performed whenever indicated. RESULTS: Nearly half (24/51; 47%) the patients had one or more extraintestinal manifestations; these included pulmonary function abnormalities (14 patients; 27%), sacroiliitis (8; 16%), arthritis (5; 10%), ocular complications (4; 8%), and pyoderma gangrenosum and Budd-Chiari syndrome (one patient each). Of the 14 (27%) patients who had abnormal pulmonary function, isolated PFT abnormalities were seen in 8 (restrictive pattern in 7, obstructive pattern in 1), decreased DLCO in four, and both of the above in two. All patients with decreased DLCO (n=6) were asymptomatic and had normal chest X-ray and HRCT chest. Thirteen (25%) patients had thrombocytosis, 19 (37%) had increased fibrinogen level, and one patient had decreased antithrombin level. Disease activity had significant association with decreased DLCO (p=0.008), increased platelet count (p<0.0001), increased fibrinogen level (p=0.016), low antithrombin levels (p=0.046) and arthritis (p=0.002). CONCLUSION: Extraintestinal manifestations of IUC were seen in 47% of patients. Asymptomatic pulmonary interstitial involvement was seen in 12%, more often among patients with active disease.

Adult↗