Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and ...Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.展开更多
Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patient...Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.展开更多
AIM: To compare the efficacy and safety of yttrium-90 radioembolization(Y90RE) and transarterial chemoembolization(TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scie...AIM: To compare the efficacy and safety of yttrium-90 radioembolization(Y90RE) and transarterial chemoembolization(TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scientific databases. When there was no statistically significant heterogeneity, pooled effects were calculated using a fixed-effects model by means of Mantel-Haenszel test, otherwise, a random-effects model was used with Der Simonian and Laird test. Summary estimates were expressed in terms of odds ratios(ORs) and 95%CI. The probability of publication bias was assessed using funnel plots and with Begg and Mazumdar's test. Sensitivity analysis was finally conducted using the method of excluding extreme data.RESULTS: A total of 10 studies were analyzed, of which 2 randomized controlled trials. Survival rate(SR) assessed at 1 year showed an absolute similarity between the two treatment groups(OR = 1.01, 95%CI: 0.78-1.31, P = 0.93). As long as time elapsed since the treatment, ORs for survival rate tended to significantly increase, thus meaning better long-term outcomes in patients who underwent Y90RE(2-year SR: OR = 1.43, 1.08-1.89, P = 0.01; 3-year SR: OR = 1.48, 1.03-2.13, P = 0.04). Meta-analysis of plotted hazard ratios(HRs) determined a non-significant overall estimate in favor of Y90RE(HR = 0.91, 0.80-1.04, P = 0.16). Y90 RE showed a statistically significant benefit as compared to TACE in terms of higher progression-free survival rateassessed at 1 year(OR = 1.67; 95%CI: 1.10-2.55; P = 0.02). Pooled analyses do not revealed a statistically significant increase in OR for tumor objective responses after Y90 RE with respect to TACE(OR = 1.22, 95%CI: 0.69-2.16, P = 0.50). A non-significant trend in favor of Y90 RE was observed according to adverse event rate(OR = 0.70, 0.38-1.30, P = 0.26).CONCLUSION: Our meta-analysis reveals that Y90 RE and TACE show similar effects in terms of survival, response rate and safety profile, although tumor progression is delayed after radioembolization.展开更多
AIM: To assess the prevalence of clinically signifi cant lesions in patients with minimal bright red bleeding per rectum (BRBPR). METHODS: Consecutive outpatients prospectively underwent colonoscopy at Loghman Hakim H...AIM: To assess the prevalence of clinically signifi cant lesions in patients with minimal bright red bleeding per rectum (BRBPR). METHODS: Consecutive outpatients prospectively underwent colonoscopy at Loghman Hakim Hospital, Tehran. Minimal BRBPR was defi ned as small amounts of red blood after wiping or in the toilet bowl. Patients with the following alarm signs were excluded: Positive personal history of colorectal neoplasms or inflamma-tory bowel disease (IBD), positive fi rst degree family history of colorectal neoplasms, history of altered bow- el habits, recent signifi cant weight loss, and presence of iron defi ciency anemia. Neoplastic polyps, colorectal carcinoma, and IBD were def ined as signif icant lesions. RESULTS: A total of 402 patients (183 female and 219 male, aged 43.6 ± 15.7 years) were studied. Hemorrhoids (54.2%), anal fi ssures (14.2%) and ul-cerative colitis (14.2%) were the most common lesions and colonoscopy was normal in 8.0%. Signifi cant le-sions were found in 121 (30.1%) patients, including 26 patients (6.5%) with adenocarcinoma and 30 (7.5%) with adenomatous polyps. Almost all patients with signifi cant lesions had at least one lesion in the distal colon; an adenocarcinoma and an adenomatous polyp in the proximal colon were found in 2 patients with hemorrhoids. CONCLUSION: Flexible sigmoidoscopy appears to be sufficient for the evaluation of average risk patients with minimal BRBPR. Rigid sigmoidoscopy may be used as an alternative in patients less than 40 years of age in settings where the former is not available. Thechoice of colonoscopy over flexible sigmoidoscopy in patients aged over 50 years should be individualized.展开更多
An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between i...An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen(HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B.This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection(Group A,n = 21) and inactive HBsAg carriers(Group B,n = 13).Serum cytokines [interferon(IFN)-γ,tumor necrosis factor-α,interleukin(IL)-1b,IL-4,IL-12,IL-10,IL-2,IL-5,IL-8] were analyzed by using flow cytometry.Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inac-tive carriers(P = 0.048 and P = 0.008,respectively).In HBeAg-negative chronic active hepatitis B patients,a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted(P = 0.021).In conclusion,patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile.Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.展开更多
AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four insti...AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration （3.6, 6.7 and 14.6 wk, P = 0.03, RR： 0.415, 95% CI：0.188-0.918）.CONCLUSION： Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.展开更多
AIM： Endoscopic sphincterotomy （ES） is a well-established therapeutic modality for the removal of common bile duct （CBD） stones. Alter ES there are still around 10% of patients that experience recurrent CBD stone...AIM： Endoscopic sphincterotomy （ES） is a well-established therapeutic modality for the removal of common bile duct （CBD） stones. Alter ES there are still around 10% of patients that experience recurrent CBD stones. The aim of this study is to investigate the composition of CBD stones before and alter ES and its clinical significance in Chinese patients.METHODS： From January 1996 to December 2003, 735 patients with CBD stones received ES at Kaohsiung Veterans General Hospital and stone specimens from 266 patients were sent for analysis. Seventy-five patients had recurrent CBD stones and stone specimens from 44 patients were sent for analysis. The composition of the stones was analyzed by infrared （IR） spectrometry and they were classified as cholesterol or bilirubinate stones according to the predominant composition. Clinical data were analyzed.RESULTS： In the initial 266 stone samples, 217 （82%） were bilirubinate stones, 42 （16%） were cholesterol stones,3 were calcium carbonate stones, 4 were mixed cholesterol and bilirubinate stones. Patients with bilirubinate stones were significantly older than patients with cholesterol stones （66＋13 years vs 56＋17 years, P = 0.001）. In the 44 recurrent stone samples, 38 （86%） were bilirubinate stones, 3 （7%） were cholesterol stones, and 3 were mixed cholesterol and bilirubinate stones. In 27 patients, both initial and recurrent stone specimens can be obtained,23 patients had bilirubinate stones initially and 2 became cholesterol stones in the recurrent attack. In the four patients with initial cholesterol stones, three patients had bilirubinate stones and one patient had a cholesterol stone in the recurrent attack.CONCLUSION： Bilirubinate stone is the predominant composition of initial or recurrent CBD stone in Chinese patients, The composition of CBD stones may be different from initial stones afl：er ES,展开更多
Arterioportal fistula(APF)is a rare cause of portal hypertension and may lead to death.APF can be congenital,post-traumatic,iatrogenic(transhepatic intervention or biopsy)or related to ruptured hepatic artery aneurysm...Arterioportal fistula(APF)is a rare cause of portal hypertension and may lead to death.APF can be congenital,post-traumatic,iatrogenic(transhepatic intervention or biopsy)or related to ruptured hepatic artery aneurysms.Congenital APF is a rare condition even in children.In this case report,we describe a 73-year-old woman diagnosed as APF by ultrasonography,computed tomography,and hepatic artery selective arteriography.The fistula was embolized twice but failed,and she still suffered from alimentary tract hemorrhage.Then,selective arteriography of the hepatic artery was performed again and venae coronaria ventriculi and short gastric vein were embolized.During the 2-year follow-up,the patient remained asymptomatic.We therefore argue that embolization of venae coronaria ventriculi and short gastric vein may be an effective treatment modality for intrahepatic APF with severe upper gastrointestinal bleeding.展开更多
Oxidative stress stemming from tissue exposure to constant hyperglycemia is one of the major pathogenetic pathways of diabetic macro-and microvascular complications. Diabetic polyneuropathy, commonly manifesting as di...Oxidative stress stemming from tissue exposure to constant hyperglycemia is one of the major pathogenetic pathways of diabetic macro-and microvascular complications. Diabetic polyneuropathy, commonly manifesting as distal,symmetrical sensorimotor polyneuropathy, is characterized by progressive severity of symptoms, with rates analogous to the quality of glycemic control achieved by the patients and physicians. Palliative care with analgesics and aggressive glycemic control often improve quality of life in the absence of causative treatment. Currently, there is a growing body of evidence indicating the role of microRNAs in the pathogenesis of diabetic complications, with emphasis on diabetic nephropathy and neuropathy. Therefore, in this review, we aim to explore the role of microRNAs and their polymorphisms in the pathophysiology of diabetic polyneuropathy, as well as, the possibility of novel diagnostic and therapeutic applications by epigenetic profiling and manipulation.展开更多
AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor mo...AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor （GM- CSF） and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS： Co-vaccination of DNA encoding GM-CSF and Fit-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4＋ T cell proliferation to this protein, Vaccination with DNA encoding GM-CSF and FIt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs, This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo, Following inoculation with plasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell （DC） and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION： Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.展开更多
This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with ...This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with chronic myocardial infarction and left ventricular dysfunction were employed for identification of viable myocardium by cine MRI during dobutamine infusion. All patients underwent coronary angiography and left ventriculography, 18 FDG PET, MRI at rest and stress.The systolic wall thickening measured at rest and during stress was compared with the results of 18 FDG PET, respectively. Results. A significant difference of either dobutamine induced systolic wall thickening (SWth stress ) or dobutamine induced contractile reserve (ΔSWth= SWth stress - SWth rest ) was present between viable and scar regions (1 0±0 3 versus -0 3 ±0 1, P<0 01; 1 0±0 3 versus -0 2±0 2, P<0 01). Conclusions. Dobutamine induced contractile reserve can be predicted in the regions of akinesia or dyskinesia at rest when systolic wall thickening was 1 0 mm during dobutamine stimulation.展开更多
AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carc...AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.展开更多
OBJECTIVE: To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A (No- go-A), and its associated signaling molecule, low-af- finity neurotr...OBJECTIVE: To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A (No- go-A), and its associated signaling molecule, low-af- finity neurotrophin receptor p75 (p75TR), in rats with cerebral ischemic stroke (CIS), with the aim of exploring the possible mechanism of tonifying liver and kidney-essence herbs in recovery following in- jury to the central nervous system. METHODS: A cerebral ischemic stroke model in SD rats was established with the suture-occlusion method. Successful model rats were divided into placebo and herb groups at random; sham-operat- ed and control groups were set up simultaneously.Each of these groups was divided into six sub- groups at random. Expression of Nogo-A and p75TR was evaluated with immunofluorescence microsco- py at days 3, and weeks1, 2, 3, 4 and 8 after adminis- tration. RESULTS: Tonifying liver and kidney-essence herbs suppressed the expression of Nogo-A and p75T (P〈0.05 and P〈0.01, respectively). CONCLUSION: Suppressing the expression of No- go-A and p75NTR is possibly one of the mechanisms underlying the ability of tonifying liver and kid- ney-essence herbs to promote recovery of the in- jured central nervous system.展开更多
AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and...AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS： The fusion protein was constructed and high efficiently expressed with yields up to 102 ±4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy （VH） and light （VL） domains of monoclonal antibody （mAb） 520C9 directed against the human HER-2/neu （c-erbB2） proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL- 2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION： The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means.of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity.展开更多
Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of...Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.展开更多
Abnormal connections between the ascending aortaand the cardiac chambers are rare, especially in thecontext of right-sided infective endocarditis(IE). Trans-thoracic echocardiography(TTE) with color-flow Dop-pler, tra...Abnormal connections between the ascending aortaand the cardiac chambers are rare, especially in thecontext of right-sided infective endocarditis(IE). Trans-thoracic echocardiography(TTE) with color-flow Dop-pler, transesophageal echocardiography(TEE), or bothmay be required for diagnosis. We present the case ofa woman admitted with right-sided heart failure(HF)symptoms. She had a previous history of tricuspid valveIE 30 years ago. TTE and TEE revealed an aorto-rightatrium fistula located just under the non-coronary cuspinto the right atrium at the level of the previously af-fected tricuspid valve. The Patient refused surgery andwas discharged home on HF medications. She has beenstable for the last 3 years. The peculiarity of this caseis the late symptomatic presentation of the aorto-atrialfistula and the unusual association to tricuspid valve IE.展开更多
Antiphospholiipid syndrome(APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies(a PL),that leads to recurrent pregnancy loss and thrombosis.Despite limited evidence,it ...Antiphospholiipid syndrome(APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies(a PL),that leads to recurrent pregnancy loss and thrombosis.Despite limited evidence,it is clear that there are both inherited and acquired components of the ontogeny of these antibodies.Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS,particularly human leukocyte antigen associations.Similarly,both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on a PL production.Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry,cryptic autoantigens exposure and apoptosis.In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.展开更多
We investigated whether the observed protective effect of hyperlipidemia is stronger in patients who take statins and, if so, whether that effect is likely due to patient characteristics associated with statin use. In...We investigated whether the observed protective effect of hyperlipidemia is stronger in patients who take statins and, if so, whether that effect is likely due to patient characteristics associated with statin use. In-hospital complications and long-term outcomes of patients with hyperlipidemia(cholesterol level ≥240 mg/dl) undergoing percutaneous coronary interventions(PCI) on statins(group Ia, n=2,052) and not on statins(group Ib, n=1,650) were compared with 726 patients with lower cholesterol levels(group Ⅱ). Despite a higher prevalence of co-morbidities and worse angiographic characteristics in patients with hyperlipidemia, patients in group Ia had significantly lower in-hospital mortality(0%vs 2%in the other 2 groups, p< 0.001), a lower increase in the postprocedure creatine kinase-MB fraction(14%vs 27%in group Ib and 28%in group Ⅱ, p< 0.001), and fewer PCI complications(15%vs 30%in groups Ib and Ⅱ, p< 0.001). After adjustment, patients in group Ia had a significant decrease in complications(odds ratio 0.72, 95%confidence interval 0.65 to 0.92, p=0.009). In contrast, those in group Ib had outcomes similar to those of patients with lower cholesterol. After application of propensity analysis to adjust for the likelihood of receiving statins based on clinical, angiographic, and procedural characteristics, group Ia had fewer in-hospital complications(odds ratio 0.75, 95%confidence interval 0.62 to 0.90, p=0.002) and lower in-hospital mortality(odds ratio 0.32, 95%confidence interval 0.12 to 0.84, p= 0.021). After successful PCI, overall survival after dismissal and survival free of myocardial infarction and target vessel revascularization were similar. In conclusion, hyperlipidemia per se is not associated with lower in-hospital complications after PCI. The benefit is largely limited to patients on statin treatment.展开更多
Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differen...Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.展开更多
文摘Apoptosis is central for the control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death inducing ligands CD95/Fas, TRAIL and TNFα occur. Nevertheless, HCV infection persists in the majority of patients. The impact of apoptosis in chronic HCV infection is not well understood. It may be harmful by triggering liver fibrosis, or essential in interferon (IFN) induced HCV elimination. For virtually all HCV proteins, pro- and anti-apoptotic effects have been described, especially for the core and NS5A protein. To date, it is not known which HCV protein affects apoptosis in vivo and whether the infectious virions act pro- or anti- apoptotic. With the availability of an infectious tissue culture system, we now can address pathophysiologically relevant issues. This review focuses on the effect of HCV infection and different HCV proteins on apoptosis and of the corresponding signaling cascades.
文摘Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.
文摘AIM: To compare the efficacy and safety of yttrium-90 radioembolization(Y90RE) and transarterial chemoembolization(TACE) in hepatocellular carcinoma patients. METHODS: Bibliographic research was conducted on main scientific databases. When there was no statistically significant heterogeneity, pooled effects were calculated using a fixed-effects model by means of Mantel-Haenszel test, otherwise, a random-effects model was used with Der Simonian and Laird test. Summary estimates were expressed in terms of odds ratios(ORs) and 95%CI. The probability of publication bias was assessed using funnel plots and with Begg and Mazumdar's test. Sensitivity analysis was finally conducted using the method of excluding extreme data.RESULTS: A total of 10 studies were analyzed, of which 2 randomized controlled trials. Survival rate(SR) assessed at 1 year showed an absolute similarity between the two treatment groups(OR = 1.01, 95%CI: 0.78-1.31, P = 0.93). As long as time elapsed since the treatment, ORs for survival rate tended to significantly increase, thus meaning better long-term outcomes in patients who underwent Y90RE(2-year SR: OR = 1.43, 1.08-1.89, P = 0.01; 3-year SR: OR = 1.48, 1.03-2.13, P = 0.04). Meta-analysis of plotted hazard ratios(HRs) determined a non-significant overall estimate in favor of Y90RE(HR = 0.91, 0.80-1.04, P = 0.16). Y90 RE showed a statistically significant benefit as compared to TACE in terms of higher progression-free survival rateassessed at 1 year(OR = 1.67; 95%CI: 1.10-2.55; P = 0.02). Pooled analyses do not revealed a statistically significant increase in OR for tumor objective responses after Y90 RE with respect to TACE(OR = 1.22, 95%CI: 0.69-2.16, P = 0.50). A non-significant trend in favor of Y90 RE was observed according to adverse event rate(OR = 0.70, 0.38-1.30, P = 0.26).CONCLUSION: Our meta-analysis reveals that Y90 RE and TACE show similar effects in terms of survival, response rate and safety profile, although tumor progression is delayed after radioembolization.
文摘AIM: To assess the prevalence of clinically signifi cant lesions in patients with minimal bright red bleeding per rectum (BRBPR). METHODS: Consecutive outpatients prospectively underwent colonoscopy at Loghman Hakim Hospital, Tehran. Minimal BRBPR was defi ned as small amounts of red blood after wiping or in the toilet bowl. Patients with the following alarm signs were excluded: Positive personal history of colorectal neoplasms or inflamma-tory bowel disease (IBD), positive fi rst degree family history of colorectal neoplasms, history of altered bow- el habits, recent signifi cant weight loss, and presence of iron defi ciency anemia. Neoplastic polyps, colorectal carcinoma, and IBD were def ined as signif icant lesions. RESULTS: A total of 402 patients (183 female and 219 male, aged 43.6 ± 15.7 years) were studied. Hemorrhoids (54.2%), anal fi ssures (14.2%) and ul-cerative colitis (14.2%) were the most common lesions and colonoscopy was normal in 8.0%. Signifi cant le-sions were found in 121 (30.1%) patients, including 26 patients (6.5%) with adenocarcinoma and 30 (7.5%) with adenomatous polyps. Almost all patients with signifi cant lesions had at least one lesion in the distal colon; an adenocarcinoma and an adenomatous polyp in the proximal colon were found in 2 patients with hemorrhoids. CONCLUSION: Flexible sigmoidoscopy appears to be sufficient for the evaluation of average risk patients with minimal BRBPR. Rigid sigmoidoscopy may be used as an alternative in patients less than 40 years of age in settings where the former is not available. Thechoice of colonoscopy over flexible sigmoidoscopy in patients aged over 50 years should be individualized.
文摘An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen(HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B.This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection(Group A,n = 21) and inactive HBsAg carriers(Group B,n = 13).Serum cytokines [interferon(IFN)-γ,tumor necrosis factor-α,interleukin(IL)-1b,IL-4,IL-12,IL-10,IL-2,IL-5,IL-8] were analyzed by using flow cytometry.Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inac-tive carriers(P = 0.048 and P = 0.008,respectively).In HBeAg-negative chronic active hepatitis B patients,a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted(P = 0.021).In conclusion,patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile.Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.
基金Supported by The Dong-A University Research Fund and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST R13-2002-044-05001-0)
文摘AIM： To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis （LMC） of gastric cancer.METHODS： We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS： The male-to-female ratio was 32：22, and the patients ranged in age from 28 to 78 years （median,48.5 years）. The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients （70%）.The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 （51%） of the patients were Bormann typeand 15 （33%） patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache （85%） and nausea/vomiting （58%） were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases （82%）. Intrathecal （IT） chemotherapy was administered to 36 patients-primarily methotrexate alone （61%）, but also in combi-nation with hydrocortisone/± Ara-C （39%）. The median number of IT treatments was 7 （range, 1-18）. Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients （46%） achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk （95% CI： 4.3-9.1 wk）. In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration （P = 0.038, P = 0.010, and P = 0.002, respectively）. However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration （3.6, 6.7 and 14.6 wk, P = 0.03, RR： 0.415, 95% CI：0.188-0.918）.CONCLUSION： Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.
基金Supported by the Grants From National Science Council, No.NSC 89-2314-B-075B-007, No. NSC 89-2315-13-075B-003No. NSC 90-2314-B-075B-001
文摘AIM： Endoscopic sphincterotomy （ES） is a well-established therapeutic modality for the removal of common bile duct （CBD） stones. Alter ES there are still around 10% of patients that experience recurrent CBD stones. The aim of this study is to investigate the composition of CBD stones before and alter ES and its clinical significance in Chinese patients.METHODS： From January 1996 to December 2003, 735 patients with CBD stones received ES at Kaohsiung Veterans General Hospital and stone specimens from 266 patients were sent for analysis. Seventy-five patients had recurrent CBD stones and stone specimens from 44 patients were sent for analysis. The composition of the stones was analyzed by infrared （IR） spectrometry and they were classified as cholesterol or bilirubinate stones according to the predominant composition. Clinical data were analyzed.RESULTS： In the initial 266 stone samples, 217 （82%） were bilirubinate stones, 42 （16%） were cholesterol stones,3 were calcium carbonate stones, 4 were mixed cholesterol and bilirubinate stones. Patients with bilirubinate stones were significantly older than patients with cholesterol stones （66＋13 years vs 56＋17 years, P = 0.001）. In the 44 recurrent stone samples, 38 （86%） were bilirubinate stones, 3 （7%） were cholesterol stones, and 3 were mixed cholesterol and bilirubinate stones. In 27 patients, both initial and recurrent stone specimens can be obtained,23 patients had bilirubinate stones initially and 2 became cholesterol stones in the recurrent attack. In the four patients with initial cholesterol stones, three patients had bilirubinate stones and one patient had a cholesterol stone in the recurrent attack.CONCLUSION： Bilirubinate stone is the predominant composition of initial or recurrent CBD stone in Chinese patients, The composition of CBD stones may be different from initial stones afl：er ES,
文摘Arterioportal fistula(APF)is a rare cause of portal hypertension and may lead to death.APF can be congenital,post-traumatic,iatrogenic(transhepatic intervention or biopsy)or related to ruptured hepatic artery aneurysms.Congenital APF is a rare condition even in children.In this case report,we describe a 73-year-old woman diagnosed as APF by ultrasonography,computed tomography,and hepatic artery selective arteriography.The fistula was embolized twice but failed,and she still suffered from alimentary tract hemorrhage.Then,selective arteriography of the hepatic artery was performed again and venae coronaria ventriculi and short gastric vein were embolized.During the 2-year follow-up,the patient remained asymptomatic.We therefore argue that embolization of venae coronaria ventriculi and short gastric vein may be an effective treatment modality for intrahepatic APF with severe upper gastrointestinal bleeding.
文摘Oxidative stress stemming from tissue exposure to constant hyperglycemia is one of the major pathogenetic pathways of diabetic macro-and microvascular complications. Diabetic polyneuropathy, commonly manifesting as distal,symmetrical sensorimotor polyneuropathy, is characterized by progressive severity of symptoms, with rates analogous to the quality of glycemic control achieved by the patients and physicians. Palliative care with analgesics and aggressive glycemic control often improve quality of life in the absence of causative treatment. Currently, there is a growing body of evidence indicating the role of microRNAs in the pathogenesis of diabetic complications, with emphasis on diabetic nephropathy and neuropathy. Therefore, in this review, we aim to explore the role of microRNAs and their polymorphisms in the pathophysiology of diabetic polyneuropathy, as well as, the possibility of novel diagnostic and therapeutic applications by epigenetic profiling and manipulation.
基金Supported by a grant from the Medical Faculty at the University of Heidelberg (Forschungsfrderungsprogramm der Medizinischen Fakultt). Jens Encke is supported by grant En 338/4-1 and En 338/5-1 both from the Deutsche Forschungsgemeinschaft, Bonn, Germany
文摘AIM： To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus （HCV） in a murine model. METHODS： We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor （GM- CSF） and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS： Co-vaccination of DNA encoding GM-CSF and Fit-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4＋ T cell proliferation to this protein, Vaccination with DNA encoding GM-CSF and FIt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs, This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo, Following inoculation with plasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell （DC） and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION： Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.
文摘This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with chronic myocardial infarction and left ventricular dysfunction were employed for identification of viable myocardium by cine MRI during dobutamine infusion. All patients underwent coronary angiography and left ventriculography, 18 FDG PET, MRI at rest and stress.The systolic wall thickening measured at rest and during stress was compared with the results of 18 FDG PET, respectively. Results. A significant difference of either dobutamine induced systolic wall thickening (SWth stress ) or dobutamine induced contractile reserve (ΔSWth= SWth stress - SWth rest ) was present between viable and scar regions (1 0±0 3 versus -0 3 ±0 1, P<0 01; 1 0±0 3 versus -0 2±0 2, P<0 01). Conclusions. Dobutamine induced contractile reserve can be predicted in the regions of akinesia or dyskinesia at rest when systolic wall thickening was 1 0 mm during dobutamine stimulation.
基金Supported by grants from the National Science Council No.NSC 93-2314-B-002-006, Taiwan, and grants from National Taiwan University Hospital 91-N006
文摘AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.
基金Suppored by Special Project on Traditional Chinese Medicine Science and Technology of State Administration of Traditional Chinese Medicine of the PRC(No.06-07LB21)
文摘OBJECTIVE: To observe the effect of tonifying liver and kidney-essence herbs on expression of a nerve regeneration inhibitor, Nogo for neuron A (No- go-A), and its associated signaling molecule, low-af- finity neurotrophin receptor p75 (p75TR), in rats with cerebral ischemic stroke (CIS), with the aim of exploring the possible mechanism of tonifying liver and kidney-essence herbs in recovery following in- jury to the central nervous system. METHODS: A cerebral ischemic stroke model in SD rats was established with the suture-occlusion method. Successful model rats were divided into placebo and herb groups at random; sham-operat- ed and control groups were set up simultaneously.Each of these groups was divided into six sub- groups at random. Expression of Nogo-A and p75TR was evaluated with immunofluorescence microsco- py at days 3, and weeks1, 2, 3, 4 and 8 after adminis- tration. RESULTS: Tonifying liver and kidney-essence herbs suppressed the expression of Nogo-A and p75T (P〈0.05 and P〈0.01, respectively). CONCLUSION: Suppressing the expression of No- go-A and p75NTR is possibly one of the mechanisms underlying the ability of tonifying liver and kid- ney-essence herbs to promote recovery of the in- jured central nervous system.
基金Supported by 90th Anniversary Fund of Chulalongkorn University(Ratchada phiseksomphot Endowment Fund)The Grant of Ratchadaphiseksomphot,Faculty of Medicine,Chulalongkorn University,Bangkok,Thailand
文摘AIM: To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy.
文摘AIM： To construct and produce a recombinant bispecific humanized single-chain Fv （sFv） /Interleukin-2 （IL-2） fusion protein by using mammalian cells. METHODS： The sFv/IL-2 protein was genetically engineered, and transfected to mammalian cells to determine whether the mammalian protein folding machinery can produce and secrete active sFv/IL-2 with high efficiency. RESULTS： The fusion protein was constructed and high efficiently expressed with yields up to 102 ±4.2 mg/L in culture supernatant of the stably transfected 293 cell line. This recombinant fusion protein consisted of humanized variable heavy （VH） and light （VL） domains of monoclonal antibody （mAb） 520C9 directed against the human HER-2/neu （c-erbB2） proto-oncogene product p185, and human IL-2 connected by polypeptide linker. The fusion protein was shown to retain the immunostimulatory activities of IL-2 as measured by IL- 2-dependent cell proliferation and cytotoxicity assays. In addition to its IL-2 activities, this fusion protein also possessed antigen-binding specificity against p185, as determined by indirect ELISA using p185 positive SKOV 3ip1 cells. CONCLUSION： The large-scale preparation of the recombinant humanized sFv antibody/IL-2 fusion protein is performed with 293 cells. The recombinant humanized sFv antibody/IL-2 fusion protein may provide an effective means.of targeting therapeutic doses of IL-2 to p185 positive tumors without increasing systemic toxicity or immunogenicity.
文摘Atopic dermatitis is a common diagnosis that presents a therapeutic challenge. Although multiple therapeutic modalities exist, there is no single monotherapy that has proven exceptional in ameliorating the symptoms of this disease. Current topical and systemic therapeutic options offer benefit but carry varying degrees of adverse effects that often limit their application. We present 3 patients with severe, recalcitrant atopic dermatitis successfully treated with omalizumab.
文摘Abnormal connections between the ascending aortaand the cardiac chambers are rare, especially in thecontext of right-sided infective endocarditis(IE). Trans-thoracic echocardiography(TTE) with color-flow Dop-pler, transesophageal echocardiography(TEE), or bothmay be required for diagnosis. We present the case ofa woman admitted with right-sided heart failure(HF)symptoms. She had a previous history of tricuspid valveIE 30 years ago. TTE and TEE revealed an aorto-rightatrium fistula located just under the non-coronary cuspinto the right atrium at the level of the previously af-fected tricuspid valve. The Patient refused surgery andwas discharged home on HF medications. She has beenstable for the last 3 years. The peculiarity of this caseis the late symptomatic presentation of the aorto-atrialfistula and the unusual association to tricuspid valve IE.
文摘Antiphospholiipid syndrome(APS) is an autoimmune disease characterized by the pathological action of antiphospholipid antibodies(a PL),that leads to recurrent pregnancy loss and thrombosis.Despite limited evidence,it is clear that there are both inherited and acquired components of the ontogeny of these antibodies.Animal genetic studies and human familial and population studies highlight the influence of genetic factors in APS,particularly human leukocyte antigen associations.Similarly,both animal and human studies have reported the importance of acquired factors in APS development and infectious agents in particular have a great impact on a PL production.Bacterial and viral agents have been implicated in the induction of autoimmune responses by various mechanisms including molecular mimicry,cryptic autoantigens exposure and apoptosis.In this review we highlight the latest updates with regards to inherited and acquired factors leading to the manufacturing of pathogenic antibodies and APS.
文摘We investigated whether the observed protective effect of hyperlipidemia is stronger in patients who take statins and, if so, whether that effect is likely due to patient characteristics associated with statin use. In-hospital complications and long-term outcomes of patients with hyperlipidemia(cholesterol level ≥240 mg/dl) undergoing percutaneous coronary interventions(PCI) on statins(group Ia, n=2,052) and not on statins(group Ib, n=1,650) were compared with 726 patients with lower cholesterol levels(group Ⅱ). Despite a higher prevalence of co-morbidities and worse angiographic characteristics in patients with hyperlipidemia, patients in group Ia had significantly lower in-hospital mortality(0%vs 2%in the other 2 groups, p< 0.001), a lower increase in the postprocedure creatine kinase-MB fraction(14%vs 27%in group Ib and 28%in group Ⅱ, p< 0.001), and fewer PCI complications(15%vs 30%in groups Ib and Ⅱ, p< 0.001). After adjustment, patients in group Ia had a significant decrease in complications(odds ratio 0.72, 95%confidence interval 0.65 to 0.92, p=0.009). In contrast, those in group Ib had outcomes similar to those of patients with lower cholesterol. After application of propensity analysis to adjust for the likelihood of receiving statins based on clinical, angiographic, and procedural characteristics, group Ia had fewer in-hospital complications(odds ratio 0.75, 95%confidence interval 0.62 to 0.90, p=0.002) and lower in-hospital mortality(odds ratio 0.32, 95%confidence interval 0.12 to 0.84, p= 0.021). After successful PCI, overall survival after dismissal and survival free of myocardial infarction and target vessel revascularization were similar. In conclusion, hyperlipidemia per se is not associated with lower in-hospital complications after PCI. The benefit is largely limited to patients on statin treatment.
文摘Some authors have used sebaceous epithelioma as a synonym for basal cell carcinoma (BCC) with sebaceous differentiation. However, our reviewof the literature revealed that definite cases of BCC with sebaceous differentiation that provide adequate clinical and histopathologic information are scarce. We present the case of a 72-year-old woman with a pigmented nodular lesion on her right ala nasi region, clinically diagnosed as pigmented BCC. Histopathologically, this nodular lesion, which was completely excised, showed typical features of BCC. It was noteworthy that within one aggregation of the presented BCC, tiny and small duct-like structures lined by cornified layers with a crenulated inner surface were seen. Vacuolated cells were scattered within a few aggregations, and they had foamy, bubbly cytoplasm and starry nuclei. The vacuolated cells were immunohistochemically positive for epithelial membrane antigen (EMA). These histopathologic findings demonstrated unquestionable sebaceous differentiation in this BCC, namely BCC with sebaceous differentiation, which should be distinguishable from both sebaceoma and sebaceous carcinoma. The small duct-like structures lined by eosinophilic cuticle, indicating apocrine differentiation, were also observed in this BCC.
