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991.
Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. 总被引:6,自引:0,他引:6 下载免费PDF全文
Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated. 相似文献
992.
A. Zarzavadjian Le Bian C. Denet N. Tabchouri H. Levard R. Besson T. Perniceni R. Costi P. Wind D. Fuks B. Gayet 《Techniques in coloproctology》2018,22(3):215-221
Background
Among the criteria used to diagnose metabolic syndrome (MS), obesity and diabetes mellitus (DM) are associated with poor postoperative outcomes following colectomy. MS is also associated with colorectal cancer (CRC) and diverticulosis, both of which may be treated with colectomy. However, the effect of MS on postoperative outcomes following laparoscopic colectomy has yet to be clarified.Methods
In an academic tertiary hospital, data from all consecutive patients undergoing laparoscopic colectomy from 2005 to 2014 were prospectively recorded and analysed. Patients presenting with MS [defined by the presence of three or more of the following criteria: elevated blood pressure, body mass index?>?28 kg/m2, dyslipidemia (decreased serum HDL cholesterol, increased serum triglycerides) and increased fasting glucose/DM] were compared with patients without MS regarding peri-operative outcome [mainly anastomotic leaks, severe postoperative complications (Clavien–Dindo III and IV)] and mortality.Results
Overall, 1236 patients were included: 508 (41.1%) right colectomies and 728 (58.9%) left colectomies. Seven hundred seventy-two (62.4%) of these procedures were performed for CRC. MS was diagnosed in 85 (6.9%) patients, who were significantly older than the others (70 vs. 64.2 years, p?<?0.001), and presented with more cardiac comorbidities (p?<?0.001). MS was associated with increased blood loss (122.5 vs. 79.9 mL p?=?0.001) and blood transfusion requirement (5.9 vs. 1.7%, p?=?0.021). The anastomotic leak rate was 6.6% (with 2.2% of anastomotic leaks requiring surgical treatment), and the overall reoperation rate was 6.9%. The incidence of severe postoperative complications was 11.5%, and the overall mortality rate 0.6%. No differences were found between the groups in overall postoperative morbidity and mortality. Median length of stay was similar in both groups (7 days).Conclusions
MS does not jeopardize postoperative outcomes following laparoscopic colectomy.993.
Pietro Mesirca Isabelle Bidaud Fran?ois Briec Stéphane Evain Angelo G. Torrente Khai Le Quang Anne-Laure Leoni Matthias Baudot Laurine Marger Antony Chung You Chong Jo?l Nargeot Joerg Striessnig Kevin Wickman Flavien Charpentier Matteo E. Mangoni 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(7):E932-E941
Dysfunction of pacemaker activity in the sinoatrial node (SAN) underlies “sick sinus” syndrome (SSS), a common clinical condition characterized by abnormally low heart rate (bradycardia). If untreated, SSS carries potentially life-threatening symptoms, such as syncope and end-stage organ hypoperfusion. The only currently available therapy for SSS consists of electronic pacemaker implantation. Mice lacking L-type Cav1.3 Ca2+ channels (Cav1.3−/−) recapitulate several symptoms of SSS in humans, including bradycardia and atrioventricular (AV) dysfunction (heart block). Here, we tested whether genetic ablation or pharmacological inhibition of the muscarinic-gated K+ channel (IKACh) could rescue SSS and heart block in Cav1.3−/− mice. We found that genetic inactivation of IKACh abolished SSS symptoms in Cav1.3−/− mice without reducing the relative degree of heart rate regulation. Rescuing of SAN and AV dysfunction could be obtained also by pharmacological inhibition of IKACh either in Cav1.3−/− mice or following selective inhibition of Cav1.3-mediated L-type Ca2+ (ICa,L) current in vivo. Ablation of IKACh prevented dysfunction of SAN pacemaker activity by allowing net inward current to flow during the diastolic depolarization phase under cholinergic activation. Our data suggest that patients affected by SSS and heart block may benefit from IKACh suppression achieved by gene therapy or selective pharmacological inhibition.Pacemaker activity of the sinoatrial node (SAN) controls heart rate under physiological conditions. Abnormal generation of SAN automaticity underlies “sick sinus” syndrome (SSS), a pathological condition manifested when heart rate is not sufficient to meet the physiological requirements of the organism (1). Typical hallmarks of SSS include SAN bradycardia, chronotropic incompetence, SAN arrest, and/or exit block (1–3). SSS carries incapacitating symptoms, such as fatigue and syncope (1–3). A significant percentage of patients with SSS present also with tachycardia-bradycardia syndrome (3). SSS can also be associated with atrioventricular (AV) conduction block (heart block) (1–3). Although aging is a known intrinsic cause of SSS (4), this disease appears also in the absence of any associated cardiac pathology and displays a genetic legacy (1, 2). Heart disease or drug intake can induce acquired SSS (2). Symptomatic SSS requires the implantation of an electronic pacemaker. SSS accounts for about half of all pacemaker implantations in the United States (5, 6). The incidence of SSS has been forecasted to increase during the next 50 y, particularly in the elder population (7). Furthermore, it has been estimated that at least half of SSS patients will need to be electronically paced (7). Although pacemakers are continuously ameliorated, they remain costly and require lifelong follow-up. Moreover, the implantation of an electronic pacemaker remains difficult in pediatric patients (8). Development of alternative and complementary pharmacological or molecular therapies for SSS management could improve quality of life and limit the need for implantation of electronic pacemakers.Recently, the genetic bases of some inherited forms of SSS have been elucidated (recently reviewed in 1, 9) with the discovery of mutations in genes encoding for ion channels involved in cardiac automaticity (4, 9, 10). Notably, loss of function of L-type Cav1.3 Ca2+ channels is central in some inherited forms of SSS. For instance, loss of function in Cav1.3-mediated L-type Ca2+ (ICa,L) current causes the sinoatrial node dysfunction and deafness syndrome (SANDD) (10). Affected individuals with SANDD present with profound deafness, bradycardia, and dysfunction of AV conduction (10). Mutation in ankyrin-B causes SSS by reduced membrane targeting of Cav1.3 channels (11). The relevance of Cav1.3 channels to SSS is demonstrated also by work on the pathophysiology of congenital heart block, where down-regulation of Cav1.3 channels by maternal Abs causes heart block in infants (12). Additionally, recent data show that chronic iron overload induces acquired SSS via a reduction in Cav1.3-mediated ICa,L (13).In mice and humans, Cav1.3 channels are expressed in the SAN, atria, and the AV node but are absent in adult ventricular tissue (14, 15). Cav1.3-mediated ICa,L plays a major role in the generation of the diastolic depolarization in SAN and AV myocytes, thereby constituting important determinants of heart rate and AV conduction velocity (14, 16). The heart rate of mice lacking Cav1.3 channels (Cav1.3−/− mice) fairly recapitulates the hallmarks of SSS and associated symptoms, including bradycardia and tachycardia-bradycardia syndrome (17, 18). In addition, severe AV dysfunction is recorded in Cav1.3−/− mice to variable degrees. Typically, these mice show first- and second-degree AV block (16, 17, 19). Complete AV block with dissociated atrial and ventricular rhythms can also be observed in these animals. The phenotype of Cav1.3−/− mice thus constitutes a unique model for developing new therapeutic strategies against SSS (10).The muscarinic-gated K+ channel (IKACh) is involved in the negative chronotropic effect of the parasympathetic nervous system on heart rate (20, 21). Two subunits of the G-protein activated inwardly rectifying K+ channels (GIRK1 and GIRK4) of the GIRK/Kir3 subfamily assemble as heterotetramers to form cardiac IKACh channels (22). Indeed, both Girk1−/− and Girk4−/− mice lack cardiac IKACh (20, 21, 23). We recently showed that silencing of the hyperpolarization-activated current “funny” (If) channel in mice induces a complex arrhythmic profile that can be rescued by concurrent genetic ablation of Girk4 (24). In this study, we tested the effects of genetic ablation and pharmacological inhibition of IKACh on the Cav1.3−/− mouse model of SSS. We found that Girk4 ablation or pharmacological inhibition of IKACh rescues SSS and AV dysfunction in Cav1.3−/−. Thus, our study shows that IKACh targeting may be pursued as a therapeutic strategy for treatment of SSS and heart block. 相似文献
994.
995.
Eugenia Sánchez Rodríguez Raquel Ríos León Francisco Mesonero Gismero Agustín Albillos Antonio Lopez-Sanroman 《Gastroenterologia y hepatologia》2018,41(10):629-635
Introduction
Thiopurine therapy can be optimised by determining the concentration of the drug's metabolites.Patients and methods
Retrospective analysis on a prospective database of 31 patients with inflammatory bowel disease who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in accordance with the results. Clinical response was reassessed after six months.Result
Despite the appropriate theoretical dose of thiopurines being administered, the dose was insufficient in 45.6% of patients (nonadherence to treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug was metabolised by other metabolic pathways. After treatment was optimised based on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while 74.2% of cases (23/31) were managed through dose optimisation alone.Discussion
Monitoring thiopurine metabolite levels may help clinicians to assess non-responsive patients before adding or switching to another drug (generally a biological agent), thereby avoiding any additional costs or potential toxicity. This strategy may also help to identify patients receiving an insufficient dose and those with an alternative metabolic pathway, who could be candidates for low-dose AZA with allopurinol, as well as patients who are suspected of being non-adherent. In three out of four patients, switching to a biological agent can be avoided. 相似文献996.
997.
998.
Jiang-Feng Mao Hong-Li Xu Jin Duan Rong-Rong Chen Li Li Bin Li Min Nie Le Min Hong-Bing Zhang Xue-Yan Wu 《Asian journal of andrology》2015,17(3):497-502
Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l-1
vs 0.4 ± 0.4 IU l−1, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l−1
vs 1.9 ± 1.1 IU l−1, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. 相似文献
999.
1000.
目的探讨妇科腹腔镜手术的并发症及处理措施。方法对我院2005年1月~2014年5月9208例妇科腹腔镜手术的临床资料进行回顾性分析。结果发生并发症9例,发生率0.1%(9/9208)。3例大血管破裂术中发现,间断缝合修补,术后生命体征平稳;肠管损伤1例,术后第5天发现,经阴道行直肠阴道瘘修补术;输尿管损伤3例,1例术中发现,即行输尿管移植术,其余2例术后1~2周发现,术后2个月余行开腹输尿管膀胱植入术;膀胱损伤2例,均为术中发现,腹腔镜下行膀胱修补术。9例术后3个月随访恢复好。结论术中应仔细解剖,手术结束前常规查看输尿管蠕动及膀胱情况,检查导尿袋尿是否红色及有无气体,怀疑肠道损伤可肛门直肠充气看盆腔有无水泡产生。大血管损伤应保持镇定,一般可以在腹腔镜下行缝合术。 相似文献