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Proportion of ground-glass opacity on high-resolution computed tomography in clinical T1 N0 M0 adenocarcinoma of the lung: A predictor of lymph node metastasis.

OBJECTIVE: In patients with clinical T1 N0 M0 lung adenocarcinoma, we investigated whether the proportion of ground-glass opacity area measured on high-resolution computed tomography was valuable for predicting the existence of lymph node metastasis, lymphatic invasion, or vascular invasion. METHODS: Between 1994 and 1999, 111 patients with clinical stage IA adenocarcinoma underwent surgical resection of the lung at our hospital. Of these, 96 patients received high-resolution computed tomography of the chest, and they constituted the study population. The tumors were semiquantitatively classified into 5 groups on the basis of the proportion of ground-glass opacity area to whole tumor shadow on high-resolution computed tomography: group I, 0%; group II, 1% to 25%; group III, 26% to 50%; group IV, 51% to 75%; and group V, 76% to 100%. Correlations of computed tomographic findings, pathologic results of lymph node metastasis and lymphatic and vascular invasion, and the histologic subtype according to the new World Health Organization classification were examined. We also investigated the characteristics of the patients with ground-glass opacity areas on high-resolution computed tomography and their value for predicting lymph node metastasis. RESULTS: Among the 96 patients, 15 (15.6%) had mediastinal lymph node metastases, and 3 (3.1%) had hilar node metastases. Regarding the proportion of the ground-glass opacity area of the tumors, 15 (15.6%) tumors were classified as group V, 11 (11.5%) as group IV, 9 (9.3%) as group III, 22 (22.9%) as group II, and 39 (40.6%) as group I, respectively. Of the 18 patients with lymph node metastases, no patients were found in groups IV and V, 2 (22.2%) were found in group III, 4 (18.2%) were found in group II, and 12 (30.8%) were found in group I (trend P =. 003), respectively. Twenty-six patients classified into groups IV and V also showed neither lymphatic invasion nor recurrence. All the smaller tumors (< or =2.0 cm) in group IV or V were histologically proved to be bronchioloalveolar carcinoma. Adjusted for smoking status and other characteristics, patients without ground-glass opacity on high-resolution computed tomography had a significantly increased risk of concurrent lymph node metastasis compared with those with ground-glass opacity. CONCLUSION: In patients with clinical T1 N0 M0 adenocarcinoma, the proportion of ground-glass opacity area on thin-section computed tomography scans was a strong predictor for tumor aggressiveness and thus could be a useful index for planning limited surgical resection for these patients.

Adenocarcinoma↗

Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival.

Based on the hypothesis that features of the molecular program of normal wound healing might play an important role in cancer metastasis, we previously identified consistent features in the transcriptional response of normal fibroblasts to serum, and used this "wound-response signature" to reveal links between wound healing and cancer progression in a variety of common epithelial tumors. Here, in a consecutive series of 295 early breast cancer patients, we show that both overall survival and distant metastasis-free survival are markedly diminished in patients whose tumors expressed this wound-response signature compared to tumors that did not express this signature. A gene expression centroid of the wound-response signature provides a basis for prospectively assigning a prognostic score that can be scaled to suit different clinical purposes. The wound-response signature improves risk stratification independently of known clinico-pathologic risk factors and previously established prognostic signatures based on unsupervised hierarchical clustering ("molecular subtypes") or supervised predictors of metastasis ("70-gene prognosis signature").

Breast Neoplasms↗

Occupational risk factors for subgroups of non-Hodgkin's lymphoma.

The non-Hodgkin's lymphomas (NHL) are a diverse group of neoplasms of the lymphatic system whose incidence has been increasing in recent years. The Centers for Disease Control Selected Cancers Study, a population-based case-control study of several cancers, included a large number of cases of NHL and a pathology review, providing a rare opportunity to study risk factors for groups of NHL subtypes. We examined the relation between occupational exposures and three subgroups of NHL: small cell diffuse lymphomas (N = 185), follicular lymphomas (N = 268), and large cell diffuse lymphomas (N = 526). There were 1,659 controls available for comparison. After controlling for demographic variables and previously identified risk factors for NHL, we observed two interesting associations, one between solvent exposure and small cell diffuse lymphomas [odds ratio (OR) = 1.60; 95% confidence interval (CI) = 1.10-2.20], and the other between meat packaging/processing and follicular lymphomas (OR = 1.60; 95% CI = 0.99-2.60). The results of this exploratory analysis are primarily negative. Our lack of positive findings may indicate that the subgroups of NHL used may not be etiologically distinct and that further work needs to be done to develop an NHL classification system that is etiologically informative and useful for epidemiologic studies.

Adult↗

Molecular differential pathology of renal cell tumours.

Recent application of molecular cytogenetic techniques to the evaluation of renal cell tumours revealed four subtypes, each with a characteristic combination of genetic alterations within the chromosomal and mitochondrial DNA. The most common, nonpapillary renal cell carcinomas are characterized by the loss of chromosome 3p sequences, rearrangement of the chromosome 5q region and loss of the chromosome 14q sequences. Papillary renal cell tumours can be divided into two groups. Tumours with a combined trisomy of chromosomes 7 and 17 as well as loss of the Y chromosome are papillary renal cell adenomas. Tumours with additional trisomies such as trisomy 16, 20 or 12 are papillary renal cell carcinomas. Chromophobe renal cell carcinomas show a combination of allelic losses, which do not occur in other types of renal tumours. In addition, they have a rearrangement in the mitochondrial DNA. Renal oncocytomas are benign tumours marked by normal or abnormal karyotypes with balanced or unbalanced translocations and an altered restriction pattern of the mitochondrial DNA. Although the major cytological characteristics of renal cell tumours, such as clear, granular, chromophobe and oncocytic cell phenotypes correspond to nonpapillary, papillary and chromophobe renal cell carcinomas and renal oncocytomas, there are many cases with overlapping phenotype. Therefore, a classification of renal cell tumours based on specific genetic alterations is proposed.

Adenoma↗

Myocyte adrenoceptor signaling pathways.

Adrenoceptors (ARs), members of the G protein-coupled receptor superfamily, form the interface between the sympathetic nervous system and the cardiovascular system, with integral roles in the rapid regulation of myocardial function. However, in heart failure, chronic catecholamine stimulation of adrenoceptors has been linked to pathologic cardiac remodeling, including myocyte apoptosis and hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling to different G proteins and induction of specific signaling pathways, which is partly regulated by the subtype-specific distribution of receptors in plasma membrane compartments containing distinct complexes of signaling molecules. The Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways bring into focus the specific signaling pathways of individual AR subtypes and their relevant functions in vivo.

Animals↗

Abnormalities of cerebral perfusion in multiple sclerosis.

BACKGROUND: Measuring perfusion provides a potential indication of metabolic activity in brain tissue. Studies in multiple sclerosis (MS) have identified areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear. OBJECTIVES: This study investigated perfusion changes in differing MS clinical subgroups on or off beta-interferon therapy using a non-invasive MRI technique (continuous arterial spin labelling) to investigate whether different clinical MS subtypes displayed perfusion changes and whether this could give a further insight into the pathological mechanisms involved. METHODS: Sixty patients (21 relapsing remitting, 14 secondary progressive, 12 primary progressive, 13 benign) and 34 healthy controls were compared. Statistical parametric mapping (SPM '99) was used to investigate regional variations in perfusion in both GM and WM. Global WM perfusion was derived by segmenting WM from images using T(1) relaxation times. RESULTS: Regions of lower perfusion in predominantly GM were observed in the primary and secondary progressive cohorts, particularly in the thalamus. Increased WM perfusion was seen in relapsing remitting and secondary progressive cohorts. CONCLUSIONS: Low GM perfusion could reflect decreased metabolism secondary to neuronal and axonal loss or dysfunction with a predilection for progressive forms of MS. Increased WM perfusion may indicate increased metabolic activity possibly due to increased cellularity and inflammation. Improved methodology and longitudinal studies may enable further investigation of regional and temporal changes, and their relationship with physical and cognitive impairment.

Adolescent↗

Diabetes insipidus.

Diabetes insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. In many patients, it is caused by the destruction or degeneration of the neurons that originate in the supraoptic and paraventricular nuclei of the hypothalamus. Known causes of these lesions include: germinoma or craniopharyngioma; Langerhans cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma following surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Magnetic resonance imaging (MRI) allows identification of the posterior pituitary hyperintensity and of hypothalamic-pituitary abnormalities. Thickening of the pituitary stalk is the second most common finding on MRI scans in several local inflammatory pathologies and autoimmune diseases or germinoma, but it is not specific to any single subtype. A progressive increase in the size of the anterior pituitary gland should alert physicians to the possibility that a germinoma is present, whereas a decrease can suggest the presence of an inflammatory or autoimmune process. Most children with acquired central diabetes insipidus and a thickened pituitary stalk have anterior pituitary hormone deficiencies during follow-up. Biopsy of enlarged pituitary stalk should be reserved for patients with a hypothalamic-pituitary mass and progressive thickening of the pituitary stalk, since spontaneous recovery may occur.

Body Water↗

Development and characterization of monoclonal antibodies specific to the serotonin 5-HT2A receptor.

Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT2A receptor. To generate MAbs against 5-HT2AR, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT2AR recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT2AR, rat and human brain lysate, and lysate from cell lines transfected with 5-HT2AR cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT2AR N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT2AR in lysates from rat brain and a 5-HT2AR-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT2AR but not with recombinant 5-HT2BR and 5-HT2CR. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies.

Aged↗

Laser capsulorrhaphy for multidirectional instability of the shoulder. An outcomes study and proposed classification system.

BACKGROUND: Clinical data on the efficacy of laser capsulorrhaphy for the treatment of multidirectional instability of the shoulder are limited. HYPOTHESIS: The diagnosis of multidirectional instability includes a spectrum of pathologic symptoms that warrants subclassification; laser capsulorrhaphy alone is not uniformly effective for all subtypes. STUDY DESIGN: Retrospective review of prospectively collected data. METHODS: Twenty-five shoulders in 21 patients were treated with laser capsulorrhaphy for multidirectional instability. Functional outcomes at a mean duration of 32 months' follow-up (range, 24 to 48 months) were recorded. RESULTS: Instability recurred in 60% of patients with congenital multidirectional instability, 17% of patients with acquired multidirectional instability, and 33% of patients with posttraumatic multidirectional instability (overall recurrence rate, 40%). Generalized ligamentous laxity was a risk factor for recurrence. Patient satisfaction rates were 40%, 83%, and 22% for the congenital, acquired, and posttraumatic subgroups. Reasons for dissatisfaction included recurrent instability, persistent pain, and inability to return to athletic activity at desired capacity. The overall mean postoperative Simple Shoulder Test score was 84%. The mean postoperative numeric rating score for pain was 3.3 (10-point scale). CONCLUSIONS: Laser capsulorrhaphy may be effective for patients with acquired multidirectional instability secondary to repetitive microtrauma but is less predictable in the other subgroups.

Adolescent↗

[Role of protein kinase C isozymes in cellular functions and pathological conditions].

Protein kinase C (PKC) is a superfamily of lipid-dependent protein Ser/Thr kinases consisting of at least 10 isozymes. The present article summarizes the papers presented at the congress symposium of the 74th Annual Meeting of the Japanese Pharmacological Society, in which six special topics regarding PKC isozyme-dependent cellular functions and pathological disorders were discussed. Using a GFP-tagged PKC expression technique, each PKC subtype was suggested to vary its targeting-site in each cell in response to each stimulus and that the targeting to the specific compartment is necessary for the specific cellular responses (NS). A cardioprotective agent, JTV519, was shown to attenuate post-ischemic myocardial injury by mimicking ischemic preconditioning through specific activation of PKC delta (YK). Using an antisense technique, PKC alpha and delta/epsilon were shown to be necessary for gene expression of inducible NO synthase by interleukin-1, one of the proinflammatory cytokines, by a stimulated transactivation of NF-kappa B (TH). In canine cerebral artery, PKC delta and PKC alpha play important roles in the development and the maintenance of vasospasm induced by subarachnoid hemorrhage, respectively (SN); and stretch-induced MLC20 phosphorylation involves MLCK and PKC alpha but not PKC delta activities facilitated by inactivation of myosin phosphatase through Rho activity (KO & KN). To clarify the role of PKC isozymes in insulin resistance, the effects of insulin on glucose uptake, PKC isozyme activation and PI3K activation in rat adipocytes were shown and then platelet PKC beta activation in diabetic patients with various diabetic complications, including diabetic retinopathy, was reported (TI). These studies will promisingly open the way to a new era for the development of novel drugs controlling an isozyme-specific activity of the protein kinase C superfamily and improvement in the knowledge about the role of the protein kinase in health and disease.

Diabetes Mellitus, Type 1↗

Adenosine receptors and cardiovascular disease: the adenosine-1 receptor (A1) and A1 selective ligands.

Adenosine has often been cited as a universal retaliatory metabolite against the destructive cellular mechanisms that are initiated during metabolic/oxidative stress. Despite this billing, clinical application of adenosine has been limited to rather specific cardiovascular indications (e.g., paroxysmal supraventricular tachycardia). At least four adenosine receptor subtypes mediate the physiologic effects of adenosine, and each receptor subtype has been implicated as a target for development of agonist- and antagonist-based therapies against a wide range of disorders (cardiac arrhythmias, asthma, renal failure, and inflammation). Yet, clinical application of receptor subtype selective ligands has been very limited. The lag in clinical development of subtype selective ligands has largely been due lack of an X-ray resolved receptor structure and concomitant production of very selective agonists and antagonists. Species and tissue differences in ligand selectivity, receptor-effector coupling, and intracellular signaling also frustrate efforts in developing subtype selective therapies despite a great deal of amino acid homology across the receptor subtypes. The adenosine subtype-1 receptor (A1) has been particularly well studied in a variety of cardiovascular pathologies and a number of selective ligands for the receptor have been developed. A1 selective ligands acting as full agonists (CVT-510) or partial agonists (CVT-2759), antagonists (BG9719/CVT-124) and allosteric enhancers (PD81723) are now under preclinical scrutiny or are being developed for the clinical application in a variety of cardiovascular disorders and will be discussed herein.

Adenosine↗

Primary hypophysitis: clinical-pathological correlations.

OBJECTIVE: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized. METHODS: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases). RESULTS: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis. CONCLUSION: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed.

Adult↗

Virus characterization, clinical presentation, and pathology associated with H7N3 avian influenza in British Columbia broiler breeder chickens in 2004.

Low-pathogenicity avian influenza (LPAI) subtype H7N3 was diagnosed on a two-age broiler breeder farm in Abbotsford, British Columbia (BC), in early February 2004. The presenting complaint in the older index flock was feed refusal, with 0.5% mortality over 72 hr that resolved over the following week Ten days after the initial complaint in the index flock, a younger flock in an adjacent barn experienced an abrupt spike in mortality (25% in 48 hr). The gross lesions of tracheal hyperemia and hilar pulmonary consolidation were subtle and nonspecific, and the diagnosis of avian influenza required laboratory confirmation. Two different viruses were isolated from the index farm: a LPAI (H7N3) was isolated from the older flock and a high-pathogenicity avian influenza (HPAI) (H7N3), which had an additional 21 base insertion at the hemagglutinin-cleavage site, was isolated from the younger flock. The presence of this insertion sequence and the similarity of adjacent sequences indicate that the LPAI had mutated into HPAI at some point between the first and second barn. Despite enhanced on-farm biosecurity measures, the virus was not contained on the index farm and eventually spread to over 40 commercial poultry facilities before massive depopulation efforts enabled its eradication.

Animals↗

Flow cytometric immunophenotype of canine lymph node aspirates.

Increasing availability of reagents able to distinguish subtypes of lymphocytes and other leukocytes has enabled greater understanding of lymphocyte biology and pathology in the dog. Lymphocytes in circulation most commonly are subjected to immunophenotypic assessment by flow cytometry, but needle aspirates of lymph nodes can be similarly suitable for immunophenotypic examination. In this investigation, the feasibility of immunophenotyping samples obtained by needle aspiration of lymph nodes from 32 dogs with no physical abnormalities and 6 dogs with lymphoma was determined. In addition, samples from 6 dogs were stored overnight at 4 degrees C and reanalyzed 24 hours later. For each sample, stained smear preparations were examined microscopically for lymphocyte morphology, neoplasia, and the presence of inflammatory cells. Expression of antigens on a corresponding sample of aspirated cells was determined by flow cytometric detection of antibody binding on a minimum of 10,000 events. The distribution of data was determined with Anderson-Darling tests, and reference intervals incorporating the central 95% of values were established. Adequate samples were obtained from 30 of 32 clinically normal dogs. Immunophenotypic results after 24 hours of storage were consistent with those obtained immediately after sampling. Reference intervals for lymphocyte subsets from normal dog lymph nodes were similar to the proportions of CD3+, CD4+, CD8+, and CD21+ lymphocytes found in blood. Aspirates of enlarged lymph nodes from dogs with lymphoma were readily classified by this technique. Aspiration of lymph nodes from dogs for comprehensive analysis by flow cytometry is feasible and applicable to immunophenotyping of lymphoma.

Animals↗

t(2;5) positive lymphoma with peripheral blood involvement.

We report two cases of CD30 and t(2;5) positive lymphomas with peripheral blood (PB) involvement. Case one demonstrated the histological appearance of a diffuse large cell lymphoma with disease in the bone marrow (BM) and PB. Immunoperoxidase stains of the BM for CD30 proved to be of value in detecting disease. RT-PCR for the t(2;5) translocation product was positive in the PB, BM and lymph node. Case two had a typical anaplastic large cell lymphoma (ALCL) morphology, with a suboptimal BM biopsy, but abnormal circulating cells in the PB showing the presence of the NPM/ALK fusion product demonstrated by RT-PCR. The first case demonstrates that not all CD30 positive and t(2;5)-associated lymphomas have an anaplastic appearance. Routine staining for CD30 and EMA in BM biopsies is useful for pathological staging. The significance of the t(2;5) in defining a specific histological subtype is unclear. RT-PCR for the t(2;5) is a more sensitive test to detect disease in PB and BM as compared with light microscopy. The clinical significance of molecular staging for patients with ALCL using RT-PCR needs to be evaluated.

Adult↗

Dopamine D1-like receptor subtypes in the rat kidney: a microanatomical study.

The microanatomical localization of dopamine D1A and D1B receptor subtypes was investigated in sections of rat kidney using immunohistochemicals techniques with antidopamine D1A and D1B receptor antibodies. Microanatomical analysis was limited to the various components of nephron. Dopamine D1A receptor immunoreactivity was found primarily in the epithelium of loop of nephron (loop of Henle) and of collecting tubules. A less intense immunoreactivity was observed within proximal and distal convoluted tubules as well as in juxtaglomerular complex. Dopamine D1B receptor immunoreactivity was found primarily in proximal and distal convoluted tubules and within the juxtaglomerular complex. A less intense immunoreactivity was observed in the epithelium of collecting tubules followed by the loop of nephron. The demonstration of the localization of dopamine D1A and D1B, receptor subtypes along the nephron may contribute to better define their significance in physiological and pathological conditions.

Animals↗

Spinocerebellar ataxia type 2 in seven Korean families: CAG trinucleotide expansion and clinical characteristics.

Studies on spinocerebellar ataxias (SCA) have been hampered by a lack of disease markers. Clinical and pathological heterogeneity also made the classification unreliable. Linkage studies established that there are multiple subtypes of SCA. Five types are found to have unstable CAG expansion; the diagnosis can be established by molecular genetic study. Therefore, we systemically screened degenerative ataxia patients for these five SCA types, and identified eight patients with SCA2 (seven from six families and one sporadic case). This paper presents the clinical information on the seven patients, whose clinical information was available in detail. CAG repeat expansion in the patients ranged from 38 to 47 (normal control, 19 to 27). The onset ages ranged from 16 to 41 with 27.1 years as the mean, which correlated inversely with repeat lengths. All patients presented dysarthria and gait ataxia. Upper limb dysmetria or dysdiadochokinesia appeared later but progressed, causing severe disability. Slow saccade (4 patients in 7) and decreased DTR (4 in 7) were common. MRIs showed severe atrophy of the brainstem and cerebellum in all patients. We conclude that SCA2 is the most frequent type in Korea and carries rather pure cerebellar syndrome, slow saccade, and hyporeflexia.

Adolescent↗

Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome.

AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gamma-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, gamma-GT, TBA, IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, gamma-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-alpha levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, gamma-GT, TBA, IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01 or 140.57 +/- 70.32 vs 79.06 +/- 35.25, P < 0.05), while biliary TBIL, DBIL, gamma-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-alpha levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-alpha levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, gamma-GT, IL-6 and TNF-alpha levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-alpha levels in the cholestasis group were higher than those in the hepatitis group. Biliary IL-6 and TNF-alpha were found to be more significantly increased than serum IL-6 and TNF-alpha in IHS (P < 0.01). The biliary IL-6 and TNF-alpha levels were positively correlated with serum DBIL, TBA and gamma-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-alpha levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.

Alanine Transaminase↗