Current medical therapy of inflammatory bowel disease

INTRODUCTIONThe 1990’s have brought a significant promise and the hopefor a better and brighter future in the new millennium forpatients with inflammatory bowel disease(IBD).A betterunderstanding of the pathophysiology of IBD symptoms hasled to newer treatment modalities and streamlining oftherapy for specific subsets of patients.

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

AIM: With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so,whether these may influence functional results achieved after anti-reflux surgery.METHODS: Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients.Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery.Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick I and II-III).RESULTS: In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin I were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase I, dipeptidylpeptidase II, β-hexosaminidase B, β-mannosidase and β-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups Ⅱ and Ⅲ at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients.CONCLUSION: Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.

Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus

AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE).METHODS: Between February 1, 1997 and February 1,2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients' samples (81%). Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ (n = 8), type Ⅱ (n = 12), type Ⅲ (n = 9), and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient.These data were further analyzed to establish the correlation with tumor localization, TNM stage (lymph-node involvement), histological type (papillary, signet-ring cell,tubular), state of differentiation (good, moderate, poor),and survival (≤24 or ≥24 mo).RESULTS: In adenocarcinomas, the activity of α-mannosidase (AMAN), cathepsin B (CB) and dipeptidyl-peptidase Ⅰ (DPP Ⅰ) increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase I in addition to these three. There was a statistical correlation of AMAN,CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were significantly higher than of those who survived for 2 years or more.CONCLUSION: Adenocarcinomas of the GEJ form a homogenous group from a tumor-biochemical aspect,and differ from the biochemical characteristics of squamous cell carcinomas of the LTE on many points.When adenocarcinomas of the GEJs are examined at the preoperative phase, the ratio of the performed AMAN,CB, and DPP Ⅰ enzymatic activity of the tissue sample from the tumor and adjacent intact mucosa within 2 cm of the tumor may have a prognostic value even in the preoperative examination period, and may indicate that ranking of these patients into the neo-adjuvant treatment group should be considered.

LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma

AIM:To investigate genes around the locus D4S2964 affected by loss of heterozygosity(LOH) and their clinical implications.METHODS:Four hundred and forty single nucleotide polymorphisms(SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication.LOH of SNPs markers in 112 cases of hepatocellular carcinoma(HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray.The correlation between allelic losses with clinicopathological features and overall survival was analyzed.RESULTS:A f ine map of LOH of SNPs in genes around D4S2964 was plotted.The average frequency of LOH in genes was 0.39.A correlation between cirrhosis and the FAL index(fractional allelic loss) was found(P = 0.0202).Larger tumor size was found to be signif icantly associated with LOH in genes ADP-ribosyltransferase 3(ART3),nucleoporin 54 kDa(NUP54),scavenger receptor class B,member 2(SCARB2) and coiled-coil domain containing 158(CCDC158)(P = 0.043,P = 0.019,P = 0.001,P = 0.037,respectively).Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B(ARD1B) and septin 11(SEPT11) had a significantly lower survival rate than those with retention(P = 0.021 and P = 0.004,respectively).A Cox regression model suggested that LOH in ARD1B and SEPT11,respectively,were predictors of the overall survival in HCC(P = 0.006 and P = 0.026,respectively).CONCLUSION:LOH in genes around D4S2964 may play an important role in HCC development and progression.LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.

Reciprocal expression of TRAIL and CD95L in Th1 and Th2 cells: role of apoptosis in T helper subset differentiation

Upon activation, naive T-helper cells can differentiate into two major distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), as defined by their effector functions and cytokine secretion patterns. Cytokine milieu and costimulatory molecules have been shown to play an essential role in determining T helper differentiation. However, it is still unclear how the effects of signals of co-stimulatory molecules and cytokines are exerted during T helper differentiation. We show evidence suggesting that while cytokine signals initiate differentiation program, the selective action of death effectors determines the endpoint balance of differenti-

Antegrade pampiniform plexus venography in recurrent varicocele:Case report and anatomy review

Varicoceles are often treated with percutaneous embolization,using fibered coils and sclerosing agents,with the latter targeted at occlusion of pre-existing collateral veins.While various methods of surgical and embolization treatment are available,varicoceles may still recur from venous collateralization.We present a case,where following demonstration of complete occlusion of the right and left gonadal veins,direct puncture of the pampiniform venous plexus under ultrasound guidance revealed recurrent varicoceles supplied by anastomoses from the ipsilateral saphenous and femoral veins to the pampiniform plexus.In doing so,we describe a technique of percutaneous pampiniform venography in a case where the pertinent anatomy was not easily demonstrated by other methods.

肌肉注射alefacept治疗掌跖银屑病

Alefacept is a dimeric fusion protein that consists of the extracellular CD2-binding portion of human lymphocyte function-associated antigen-3, which is linked to the Fc segment of human IgG1.1 Alefacept inhibits T-cell activation and proliferation, and induces apoptosis of memory-effector (CD45RO+) T cells in vitro,2 limiting the inflammatory and uncontrolled keratinocyte proliferation seen in psoriatic lesions. Alefacept is the first biologic approved in the United States for the treatment of moderate to severe chronic plaque psoriasis. This report describes the use of alefacept in 2 patients with extensive and recalcitrant palmoplantar psoriasis who achieved significant improvements on alefacept therapy.

妊娠期母体血管反应性的无创超声评估:一项纵向研究

OBJECTIVE: To estimate the pattern of maternal vascular reactivity in normal a nd high-risk pregnancies using postocclusion brachial artery diameter. METHODS: Prospective, longitudinal study of 44 low-risk singleton pregnancies and 28 hi gh-risk pregnancies, defined as pregestational diabetes (n = 7), chronic hypert ension (n = 4), twin gestation (n = 6), and a previous history of preeclampsia, fetal growth restriction, or vascular disease (n = 11). During each trimester, t he brachial artery was ultrasonographically imaged above the antecubital crease. Brachial artery diameter was measured and then occluded for 5 minutes using an inflated blood pressure cuff. Changes in brachial artery diameter at 1 minute af ter occlusion were expressed as percent change from baseline and were compared a cross trimesters for both low-risk and high-risk groups, adjusting for potenti al confounders. RESULTS: Brachial artery diameters were increased after occlusio n in every trimester for all groups. For low-risk women, the degree of postoccl usion brachial artery dilatation was similar in the first and second trimesters, but was lower in the third trimester. In the first trimester, low-risk women h ad significantly greater brachial artery diameter increases at 1 minute compared with high-risk singleton pregnancies (19%compared with 12%; P < .001). Compa red with low-risk women, pregnancies complicated by pregestational diabetes or chronic hypertension had significantly smaller 1-minute brachial artery diamete r changes in the first trimester (7.0 ±0.5%, P < .001), whereas twin gestation s had greater brachial artery responses (22.9 ±6.0%, P < .001). Women with pre vious preeclampsia or vascular disease had responses similar to low-risk women. CONCLUSION: Maternal vascular reactivity as assessed by postocclusion brachial artery dilatation decreases in the third trimester in both low-risk and high-r isk women. In addition, singleton pregnancies at high risk for preeclampsia disp lay decreased brachial artery reactivity compared with low-risk women.

DiGeorge综合征伴SAPHO性骨髓炎和类肉瘤样皮炎1例

We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion developed after she was treated with isoniazid (INH) following exposure to active tuberculosis (TB). After resolution of the skin lesions, this child developed sterile hyperplastic osteomyelitis consistent with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) osteomyelitis in her right mandible triggered by an odontogenic infection. This child had congenital heart disease, dysmorphic facies, recurrent sinopulmonary infection, gastroesophgeal re- flux disease, scoliosis, reactive periostitis, and developmental delay. She had a low CD4 and CD8 T cell count with a normal 4/8 ratio, but normal cell proliferation and T cell cytokine production in response to mitogens. When she was presented with sterile osteomyelitis of right mandible, she revealed polyclonal hypergammaglobulinemia with elevated erythrocyte sedimentation rate (ESR)/ angiotensin converting enzyme (ACE) levels, but negative CRP. Autoimmune and sarcoidosis workup was negative. Inflammatory parameters gradually normalized following resolution of odontogenic infection and with the use of non- steroidal anti- inflammatory drugs (NSAIDs). The broad clinical spectrum of DGS is further expanded with the development of autoimmune and inflammatory complications later in life. This case suggests that patients with the DGS can present with unusual sterile inflammatory lesions triggered by environmental factors, further broadening the clinical spectrum of this syndrome.

减少中国快速发展城镇的室内暴露健康风险

[背景]在过去的20年,中国人口从农村向城镇大迁移。与此同时,城市住宅的特征已经发生变化,从单层或低层建筑变为高层建筑,并用许多合成材料建造和装配。其结果是室内暴露(源于室外和室内的污染物)显著改变。[目的]本文简要讨论了中国城镇化和现代化建设已经对室内暴露和公众健康产生的可能影响,旨在论证日益增加的、与这些变化相关的不良医疗费用并非不可避免,并提出降低室内有害污染物暴露所能采取的措施。[讨论]正如中国卫生部所记录的,在过去20年间城镇居民的发病率和死亡率显著增加。有证据表明,人群空气污染物暴露已经导致肺癌、心血管疾病、肺部疾病和出生缺陷的增加。无论污染物来源于室外或室内,大多数的污染物暴露发生在室内。今后,人们可以通过限制室外污染物侵入(同时充分通风提供清洁空气),尽量减少室内来源的污染物,更新与室内污染相关的政府政策,以及在建筑物设计之初注重室内空气质量等措施来减少室内暴露。[结论]采取上述建议的措施可能会显著降低发病率和死亡率,大大降低污染物所致不良健康事件相关的社会成本。