毛细支气管炎细胞因子与发病机理的研究

为了解毛支发病机理与机体免疫功能的关系，探讨环境与遗传因素对发病的影响，对３０例不同病毒感染的毛支患儿取血清及外周血单个核细胞（ＰＢＭＣ）培养，用ＥＬＩＳＡ方法测定培养上清中细胞因子及血清ＩｇＥ浓度。结果表明：①毛支急性期ＩＦＮ－γ水平降低，ＩＬ－４、ＩＬ－１０及血清ＩｇＥ水平增高。②毛支ＩＬ－４、ＩＬ－１０、ＩｇＥ水平增高与感染病毒的种类关系不明显，与机体遗传特应质有关。提示：毛支患儿存在细胞免疫功能异常，表现在细胞因子分泌紊乱。遗传因素在细胞因子分泌异常中可能有重要作用。

小儿哮喘发病机理和治疗展望

小儿哮喘发病机理和治疗展望第三军医大学大坪医院儿科（重庆，４０００４２）李华强小儿哮喘是常见的影响儿童健康和生活质量的慢性疾病。近十几年来，支气管哮喘发病机制和防治一直是研究的热门，并取得了一定的成果。１发病机理［１～４］１１遗传、环境因素哮喘是一...

药源性心力衰竭

本文结合新近的文献报道，对药源性心衰的发生机理、致病药物、临床特征及诊断与防治等问题进行总结。

AIDS and associated malignancies

AIDS associated malignancies （ARL） is a major complication associated with AIDS patients upon irnmunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy （ARV）, the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi＇s sarcoma （KS）, Hodgkin＇s disease （HD） and non-Hodgkin＇s lymphoma （NHL）. The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV- 1 seronegative patients. For example nearly haft of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus （EBV） or human herpesvirus-8 （HHV-8）/Kaposi＇s sarcoma associated herpesvirus （KSHV）. The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.

Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy

Although the aetiology of inflammatory bowel disease (IBD) remains unknown, the pathogenesis is gradually being unravelled, seeming to be the result of a combination of environmental, genetic, and immunological factors in which an uncontrolled immune response within the intestinal lumen leads to inflammation in genetically predisposed individuals. Multifactorial evidence suggests that a defect of innate immune response to microbial agents is involved in IBD. This editorial outlines the immunopathogenesis of IBD and their current and future therapy. We present IBD as a result of dysregulated mucosal response in the intestinal wall facilitated by defects in epithelial barrier function and the mucosal immune system with excessive production of cytokines growth factors, adhesion molecules, and reactive oxygen metabolites, resulting in tissue injury. Established and evolving therapies are discussed in the second part of this editorial and at the end of this section we review new therapies to modulate the immune system in patients with IBD.

Is osteoporosis a peculiar association with primary biliary cirrhosis?

AIM： （1） To compare the prevalence of osteoporosis （t-score ≤-2.5 SD） between stage IV PBC patients, and two groups of age- and sex-matched controls： one with hepatitis C virus （HCV）-related cirrhosis, and the other one consisting of a group of healthy subjects from the general population, （2） to identify the main risk factors for the development of bone loss. METHODS： Thirty-five stage IV PBC patients （mean age 52.5±10 years）, 49 females with HCV-related cirrhosis （mean age 52.9±5.8 years） and 33 healthy females （mean age 51.8±2.22 years） were enrolled in the study. Bone metabolism was evaluated by measuring serum calcium corrected for serum albumin （Ca corr.）, 25-hydroxy vitamin D （25-OH vit D）, parathyroid hormone, osteocaldn. Bone mineral density （BMD） was assessed at the lumbar spine by dual-photon X-ray absorptiometry. RESULTS： Osteoporosis was present in 5/35 PBC patients （14.2%） and in 7/49 HCV-related drrhotic patients （14.3%）, without any statistical difference between the two groups. Among healthy control subjects, none had osteoporosis. No difference was found between the three groups in serum parameters of bone metabolism. Univariate analysis showed that menopausal state and low BMI were significantly correlated with osteoporosis. Multivariate regression analysis showed that menopausal status, BMI〈23, and old age were independent variables significantly correlated with osteoporosis. CONCLUSION： PBC in itself has no negative influence on BMD. End-stage liver disease patients carry a disease-specific risk for osteoporosis, but have an effective risk of bone loss in relation to individual potential risk for each patient. A practical message should be taken into account, that is, every effort should be made to prevent osteoporosis when a patient has simple osteopenia, or if it is a woman in or near menopausal age.

Function and regulation of Aurora/Ipllp kinase family in cell division

During mitosis, the parent cell distributes its genetic materials equally into two daughter cells through chromosome segregation, a complex movements orchestrated by mitotic kinases and its effector proteins. Faithful chromosome segregation and cytokinesis ensure that each daughter cell receives a full copy of genetic materials of parent cell. Defects in these processes can lead to aneuploidy or polyploidy. Aurora/Ipl1p family, a class of conserved serine/threonine kinases, plays key roles in chromosome segregation and cytokinesis. This article highlights the function and regulation of Aurora/Ipllp family in mitosis and provides potential links between aberrant regulation of Aurora/Ipllp kinases and pathogenesis of human cancer.

Celiac disease:Prevalence,diagnosis,pathogenesis and treatment

Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.

Clinical evaluation of submucosal colonic lipomas: Decision making

Even lipomas are the most common mesenchymal benign tumors of the gastrointestinal tract, symptomatic colonic presentation is rare. Herein, we evaluated four patients suffering from various size of colonic lipomas and approached by different therapeutic modalities.

Diverticular disease of the colon:New perspectives in symptom development and treatment

Diverticular disease of the colon is a common disease worldwide.Although the disease is asymptomatic in about 70-80 % of patients,it represents,at least in Western countries,one of the most important gastrointestinal diseases in terms of direct and indirect health costs.Pathogenesis of the disease is still unknown.However,it is the result of complex interactions between colonic structure,intestinal motility,diet and genetic factors.Whilst efficacious preventive strategies remain to be identified,fibre supplementation in the diet is recommended.Why symptoms develop is still unclear.Results of recent experimental studies on irritable bowel syndrome speculated that low grade inflammation of colonic mucosa,induced by changes in bacterial microflora, could affect the enteric nervous system,which is crucial for normal gut function,thus favouring symptom development. This hypothesis could be extrapolated also for diverticular disease,since bacterial overgrowth is present,at least in a subgroup of patients.These perspectives on symptom development are reviewed and new therapeutic approaches are hypothesized.

Induction of apoptosis by artemisinin relieving the severity of inflammation in caerulein-induced acute pancreatitis

AIM： To observe the apoptosis and oncosis of pancreatic acinar cells and secondary inflammatory reaction in pancreatic tissue from rats with acute pancreatitis （AP）, and the influences of artemisinin on them.METHODS： AP was induced by 4 intraperitoneal iojections of caerulein at 1 h intervals. To induce apoptosis, solution of artemisinin （50 mg/kg） was given intraperitoneally 1, 12, 24 and 36 h after the last caerulein injection. Histological examination of impairment of pancreatic tissue and detection of serum amylase were performed to evaluate the severity of acute pancreatitis. Apoptosis and oncosis were detected with acridine orange （AO） and ethylene dibromide （EB） staining. Caspase-3 and myeloperoxidase （MPO） activity were measured by colorimetric assay. Nuclear factor-kappa B （NF-KB） activation was detected by flow cytometry. Macrophage inflammatory protein-lα（MIP-1α） protein was measured by Western blot. Interleukin- 1β（IL-1β） mRNA was detected by RT-PCR.RESULTS： Addition of artemisinin increased the number of apoptotic cells （11.7%±1.4% vs 6.3%± 0.7%, P 〈 0.05）, while reduced the number of oncotic cells （13.0% ±2.4% vs 17.5%±2.2%, P 〈 0.05）. The activity of caspase-3 speeded up （1.52±0.21 vs 1.03±0.08, P 〈 0.05）, the pancreas pathological impairment was relieved （3.0±0.5 vs 4.0± 0.5, P 〈 0.05） and the level of serum amylase decreased （5642±721 U/dL vs 7821±653 U/dL, P 〈 0.05）. The activation of NF-1α （29%±4.1% vs 42%±5.8%）, MIP-1α protein （3.7±0.5 vs 5.8±0.7）,MPO （0.52±0.06 U/g vs 0.68±0.09 U/g）, IL-1β mRNA （1.7 ±0.3 vs 2.4 ±0.4） in the apoptosis inducing group was obviously decreased （P 〈 0.05）.CONCLUSION： Inducing apoptosis can relieve pathological impairment and inflammatory reaction in AP rats.

Is the severity of obstructive sleep apnea or the magnitude of respiratory effort associated with gastroesophageal reflux?

In a recent issue ot World Journal of Gastroenterology, Demeter et al., reported that in patients having both gastro-esophageal reflux disease （GERD） and obstructive sleep apnea （OSA）, there was a positive correlation between endoscopic findings of GERD and the number of apneas and hypopneas per hour, namely apnea hypopnea index. They proposed that the severity of OSA and GERD are parallel to each other. The study of Demeter and colleagues is very important, not only for assessing reflux-induced esophageal damage in OSA,

Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis:Pathogenesis and therapeutic implications

AIM:To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC).METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n=6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential eff icacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting.RESULTS: Human acute phase NEC tissues displayed significant increases (P<0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide.CONCLUSION:LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infi ltration.

Clinical characteristics of fulminant hepatitis in pregnancy

AIM： To investigate the clinical characteristics of fulminant hepatitis in pregnancy. METHODS： We compared and analyzed the etiology, clinical characteristics, and laboratory examinations of 25 cases of fulminant hepatitis in pregnancy and 30 cases of fulminant hepatitis not in pregnancy. RESULTS： HBV infection and chronic fulminant hepatitis were most common both in the pregnant and in the non-pregnant groups. Jaundice, digestive tract symptoms, increase of bilirubin and thrombinogen activity were the main manifestations. The incidence of hepatic encephalopathy （HE） and hepato-renal syndrome （HRS） was significantly different between the two groups. The incidence of preterm labor, dead fetus and neonatal asphyxia was high. CONCLUSION： Fulminant hepatitis is likely to occur in late pregnancy wibh more severe complications, which significantly influences maternity, perinatal fetus, and newborn.

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm,was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis,the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature,including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include,total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199and CEA levels for a suspicious cystic pancreatic mass.

Outcome of lamivudine-resistant hepatitis B virus is generally benign except in cirrhotics

AIM： We set to determine factors that determine clinical severity after the development of resistance.METHODS： Thirty-five Asian patients with genotypic lamivudine resistance were analyzed in three groups： 13/35 （37%） were non-cirrhotics with normal pre-treatment ALT （Group IA）, 12/35 （34%） were non-cirrhotics with elevated pre-treatment ALT （Group IB）, and 10/35 （29%） were cirrhotics （Group II）. Patients were followed for a median of 98 wk （range 26-220） after the emergence of genotypic resistance.RESULTS： Group IA patients tended to retain normal ALT. Group IB patients showed initial improvement of ALT with lamivudine but 9/12 patients （75%） developed abnormal ALT subsequently. On follow-up however, this persisted in only 33%. Group II patients also showed improvement while on treatment, but they deteriorated with the emergence of resistance with 30% death from decompensated liver disease. Pretreatment ALT levels and CPT score （in the cirrhotic group） were predictive of clinical resistance and correlated with peak ALT levels and CPT score.CONCLUSION： The phenotype of lamivudine-resistant HBV correlated with the pretreatment phenotype. The clinical course was generally benign in non-cirrhotics. However, cirrhotics had a high risk of progression and death （30%） with the development of lamivudine resistance.

Crohn’s and colitis in children and adolescents

Crohn＇s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases （IBD）. These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn＇s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions： these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythma nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn＇s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, the- reby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult- onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn＇s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.

Acute appendicitis presenting with abdominal wall and right groin abscess:A case report

We report a case of right lower abdominal wall and groin abscess resulting from acute appendicitis. The patient was an 27-year-old man who had no apparent abdominal signs and was brought to the hospital due to progressive painful swelling of right lower abdomen and the groin for 10 d. Significant inflammatory changes of soft tissue involving the right lower trunk were noted without any apparent signs of peritonitis. Laboratory results revealed leukocytosis. Abdominal ultrasonography described the presence of abscess at right inguinal site also communicating with the intraabdominal region. Right inguinal exploration and laparotomy were performed and about 250 mL of pus was drained from the subcutaneous tissue and preperitoneal space. No collection of pus was found intraabdominally and subserous acute appendicitis was the cause of the abscess. The patient fully recovered at the end of the second post-operation week. This case reminds us that acute appendicitis may have an atypical clinical presentation and should be treated carefully on an emergency basis to avoid serious complications.

Pathogenesis of congenital pyrimidine 5′ -nucleotidase | deficiency: A study on relationship among erythrocyte morphology, enzyme protein content and activity

Objective: To further explore the mechanism of congenital pyrimidine 5'-nucleotidase I deficiency. Methods; The samples were collected from the family members of a patient with P5'N- I deficiency. The enzyme activities were measured by UMP method and the enzyme proteins were quantified by ELISA while the morphology of peripheral blood cells was observed. Results: The enzyme contents reduced as their enzyme activities decreased in the family especially in four members. There was a significant positive correlation(r =0. 955) between the activity and the content of P 5'N- I . The count of the stippling cell was varied in the family. Conclusion.- One of the reasons for congenital P5' N- I deficiency might be the deficiency in the enzyme content. The morphology of peripheral blood erythrocyte may be an assistant diagnotic index. The P5'N- I activities and contents were measured simultaneously may be a effective method in clinic diagnosis.

THE EFFECT OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION ON THE PATHOGENESIS OF ANGINA DECUBITUS

Objective. To investigate the effect of left ventricular diastolic dysfunction on the pathogenesis of angina decubitus (AD). Methods. The study population consisted of three groups: 20 individuals without cardiovascular disease were studied as group Ⅰ.Group Ⅱ included 20 patents with coronary artery disease and without AD. Thirty-one patients with AD and ejection fraction(EF)>50% were studied as group Ⅲ. Group Ⅱ and Ⅲ were matched for age, EF and extent of coronary artery disease. Results. Left ventriculography (LVG) showed that left ventricular (LV) first 1/3 filling fraction(1/3FF) was significantly lower in group Ⅲ than in group Ⅱ and Ⅰ(both P<0001),but LV late 1/3 FF was much higher in group Ⅲ than in group Ⅱ and Ⅰ(P<005, P<001). Left ventricular end-diastolic pressure(LVEDP)was markedly increased before and after LVG in group Ⅱ and Ⅲ as compared with group Ⅰ (both P<005, both P<0001). The difference of LVEDP caused by left atrial contraction (left atrial contraction pressure difference, LACPD)before and after LVG was much higher in group Ⅲ than in group Ⅰ ( P<001, P<0001). Howevere,there were significant differences in LVEDP and in LACPD between before and after LVG only in group Ⅲ (both P<001). Conclusion. The patients with AD have LV diastolic dysfunction, which may be closely related to the pathogenesis of angina decubitus.