第十一讲 阴茎硬结症 阴茎结核

1 阴茎硬结症阴茎硬结症,又名阴茎纤维性海绵体炎。本症是由法国医生Peyronie于1743年首先予以详细报道的男性生殖器官疾病,所以又可称为Peyronie病。 1.1 病因病理对本症的发病原因认识尚不明确。一般认为与维生素E缺乏、轻度外伤、硬化性炎症、退行性病变有关,也有人认为与感染及免疫紊乱的关系更为密切。本症的病理变化主要是在阴茎海绵体白膜与阴茎深筋膜之间发生的纤维性病变,并波及海绵体内及其间质。

Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

Primary sclerosing cholangitis （PSC） is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease （IBD） affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence （up to 3.6%） in Crohns disease. The strength of this association means that the vast majority （ 〉 90%） of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fitch decade of life with a strong male predominance. Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ilieitis and has a high risk of pouchitis post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis （AIH） is also more prevalent in patients with IBD, with up to 16% of patients with Autoimmune Hepatitis also having ulcerative colitis. A small subgroup of patients have a AIH-PSC overlap syndrome and the management of these patients depends on liver histology, serum IgM levels, autoantibodies, degree of biochemical cholestasis and cholangiography as some of these patients may respond to immunosupression.

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). METHODS: Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P < 0.001), obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION: The prevalence of MS, obesityand T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.

Mechanisms of biliary carcinogenesis and growth

Cholangiocarcinoma is a rare cancer originating from the neoplastic transformation of the epithelial cells (i.e. cholangiocytes) that line the biliary tract. The prognosis for patients with cholangiocarcinoma is grim due to lack of viable treatment options. The increase in world-wide incidence and mortality from cholangiocarcinoma highlights the importance of understanding the intracellular mechanisms that trigger the neoplastic transformation of cholangiocytes and the growth of biliary cancers. The purpose of the following review is to address what has been learned over the past decade concerning the molecular basis of cholangiocarcinogenesis. The material presented is divided into two sections:(1) mechanisms regulating neoplastic transformation of cholangiocytes; and (2) factors regulating cholangiocarcinoma growth. An understanding of the growth regulatory mechanisms of cholangiocarcinoma will lead to the identification of therapeutic targets for this devastating cancer.

Correlations Between Serum Uric Acid Level and Disease Activity,Intrathecal Inflammation Reactivity in Patients with Multiple Sclerosis

Objective To explore the correlations between serum uric acid （HA） levels and the clinical and cerebrospinal fluid （CSF） parameters of multiple sclerosis （MS）. Methods The medical reports of 47 MS patients admitted to Peking Union Medical College Hospi- tal during 2008 and 2010 were reviewed. And 49 age- and gender-matched cerebral infarction patients were enrolled as control. The mean serum HA level of the MS patients was compared with that of the control group. The correlations between the HA levels and the clinical parameters including gender, disease duration, relapse rate, and disease disabilities as assessed by the Expanded Disability Status Scale score, were explored. Forty-one patients had CSF examinations. The correlations between the IdA levels and the CSF parameters reflecting inflammation and tissue damage, including CSF protein, white blood cell count, oligoclonal band, 24-hour IgG index, and myelin basic protein, were also investigated. Results The mean serum HA level in the MS patients was lower than that in the control group （247.75 ± 52.59 jamol/L vs. 277.94 ± 74.33 pmol/L, P=0.025） and inversely correlated with the relapse rate （P=0.049）. MS patients with lower serum UA levels tended to have higher white blood cell counts and myelin basic protein level. But there was no correlation between CSF protein levels （r=0.165, P=0.273）, white blood cell counts （r=-0.051, P=0.732）, IgG index （r =0. 045, P=0.802）, or myelin basic protein level （r =-0.248, P=0.145） and the serum UA level, respectively. Conclusion In MS patients, UA levels might partly reflect the extent of disability and inflammation.

Fenofibrate for patients with asymptomatic primary biliary cirrhosis

AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.

Prognostic value of ^(13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure

AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival.CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease.

SIGNIFICANCE OF MMP-2 AND TIMP-2 mRNA EXPRESSIONS ON GLOMERULAR CELLS IN THE DEVELOPMENT OF GLOMERULOSCLEROSIS

Objective To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis. Methods The expressions of MMP-2, TIMP-2, and Col ⅣmRNA on cultured rat MsC stimulated by IL-1 or/and TGF-β1were investigated through Northern blot analysis. The levels of MMP-2 and TIMP-2 mRNA expressions and immunoreacti-vity of PCNA and Col Ⅳin human diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were examined by insituhybridization and immunohistochemistry, respectively. Results The levels of MMP-2, TIMP-2, and Col ⅣmRNA expressions were markedly increased on cultured rat MsC stimulated by IL-1 or/and TGF-β1. Meanwhile, upregulation of MMP-2 and TIMP-2 mRNA expressions was confirmed in diseased glomeruli from patients with various subtypes of LN, and was closely related to the positive cell number of PCNA presentation and deposition of Col Ⅳin glomeruli. Conclusion The results suggest that the over-expressions of MMP-2 and TIMP-2 mRNA on glomerular cells might play a critical role in the development of glomerulosclerosis.

Genetic epidemiology of primary sclerosing cholangitis

The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants,however,remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However,according to strict criteria for what may be denominated a susceptibility gene in complex diseases,no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC,as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).

Effects of linagliptin on inflammatory factors and arteriosclerosis in patients with newly diagnosed type 2 diabetes mellitus

In the present study,we aimed to investigate the effects of linagliptin on inflammatory factors and carotid intima-media thickness(CIMT)in newly diagnosed type 2 diabetes mellitus(T2 DM)patients with carotid atherosclerotic disease(CAD).A total of 326 patients with newly diagnosed T2 DM complicated with CAD were randomly divided into two groups.There were 163 patients in the control group,who were treated with metformin monotherapy.There were 163 patients in the experimental group,who were treated with metformin in combination with linagliptin.The CIMT before and after treatment was measured by color Doppler ultrasound,and the contents of IL-6 and IL-1βbefore and after treatment were detected by ELISA.The levels of inflammatory factors and CIMT before and after treatment were compared between the two groups,and the correlation between IL-6,IL-1βand CIMT was studied.After 24 weeks of treatment,the levels of inflammatory factors and CIMT in the experimental group were significantly lower compared with the control group(P<0.01),and the serum levels of IL-6 and IL-1βwere positively correlated with CIMT.In the present study,we concluded that linagliptin could improve the levels of inflammatory factors and CIMT in newly diagnosed T2 DM patients with CAD,and IL-6 and IL-1βmight participate in the occurrence and development of CAD by influencing CIMT.