Differential Effect of Diarrhea on FK506 Versus Cyclosporine A Trough Levels and Resultant Prevention of Allograft Rejection in Renal Transplant Recipients

Diarrhea is the most frequently reported adverse event in patients treated with mycophenolate mofetil. Twenty-six renal transplant patients on a mycophenolate mofetil-based immunosuppressive regime with persistent afebrile diarrhea were examined. Diarrhea caused a significant rise in FK-506 trough levels despite intake of stable doses, necessitating FK-506 dose reductions of 30% to obtain pre-diarrhea trough levels. In contrast, trough levels of cyclosporine A remained stable without dose adjustments. This suggests that absorption and/or metabolism is differentially altered for FK506 compared with cyclosporine A in patients with diarrhea. In nine patients mycophenolate mofetil was reduced or stopped because of persistent diarrhea without identifiable cause. This resulted in end-stage renal disease because of chronic rejection in two patients, and in acute rejection in two patients, all taking FK506 and steroids. Therefore, dose adjustments of FK506 in patients with diarrhea must be carefully monitored, especially when doses of mycophenolate mofetil are also reduced.     

双歧杆菌三联活菌肠溶胶囊联合阿奇霉素序贯疗法治疗对肺炎支原体肺炎腹泻患儿胃肠炎症的调节作用

目的观察双歧杆菌三联活菌肠溶胶囊联合阿奇霉素序贯疗法治疗对肺炎支原体肺炎腹泻患儿胃肠炎症的调节作用。 方法将肺炎支原体肺炎伴腹泻的患儿106例均分为对照组和观察组。对照组采用阿奇霉素序贯疗法治疗,观察组在对照组基础上给予双歧杆菌三联活菌肠溶胶囊治疗。比较两组疗效和肠道菌群失调发生率。比较两组胃肠激素、降钙素原(PCT)、C反应蛋白(CRP)、中性粒细胞百分比(NEUT%)、嗜酸性粒细胞计数(EOS)水平。 结果观察组总有效率高于对照组(P＜0.05)。治疗后,两组胃肠激素和PCT、CRP、NEUT%、EOS较治疗前下降(P＜0.05),且观察组低于对照组(P＜0.05)。观察组肠道菌群失调发生率低于对照组(P＜0.05)。 结论双歧杆菌三联活菌肠溶胶囊联合阿奇霉素序贯疗法治疗可减轻肺炎支原体并腹泻肺炎患儿炎症反应,调节胃肠激素,降低患儿肠道菌群失调的发生。     

High frequency of rotavirus viremia in children with acute gastroenteritis: Discordance of strains detected in stool and sera

Recently, rotavirus antigenemia and viremia have been identified in patients with acute gastroenteritis. This study examined rotavirus viremia in children hospitalized for acute gastroenteritis in order to establish its association with fecal shedding of rotavirus, infecting genotypes and antibody marker of acute infection. Thirty‐one pairs of stool–serum specimens were collected from November 2004 to February 2005 together with clinical information. All paired specimens were screened for rotavirus RNA by RT‐PCR using the VP6 gene primers. All stool and serum specimens were tested for rotavirus antigen and anti‐rotavirus IgM respectively by ELISA. Sixteen of 31 stool–serum pairs showed the presence of rotavirus RNA. Nine stool and two serum specimens were positive only by RT‐PCR. The total positivity in rotavirus RNA was significantly higher in both stools (80.6%) and sera (58.1%) than that of stool antigen (38.7%) and anti‐rotavirus IgM (25.8%) (P < 0.01). All PCR positive paired specimens were typed for the VP7 (G) and VP4 (P) genes. Five of sixteen pairs could be typed for both genes. Three of the five pairs showed concordance (G2P[4]/G2P[4]) while two showed discordance (G12P[8]/G2P[4], G8P[4]/G2P[4]) in the genotypes detected in stool and serum specimens respectively. The study documents a high frequency of rotavirus viremia in patients with acute diarrhea. The discordance of rotavirus strains at the genotypic level in the serum and stool of individual patients with diarrhea suggests the susceptibility of extra‐intestinal sites for rotavirus infection and the possibility of differential dissemination of rotavirus strains from the intestine. J. Med. Virol. 80:2169–2176, 2008. © 2008 Wiley‐Liss, Inc.     

Rapid detection of Clostridium difficile toxin A in stool specimens

Objective: To evaluate a rapid (15-min) enzyme immunoassay in the format of an individual cassette (ImmunoCard toxin A, Meridian, BMD, Marne-la-Vallée, France) for the detection of Clostridium difficile toxin A in stool specimens.
Methods: We compared this new test with the cytotoxicity assay using MRC-5 cells, the ToxA test (TechLab, BioWhittaker, Fontenay-sous-bois, France) and toxigenic culture for the diagnosis of C. difficile -associated diseases (CDAD). A total of 236 stool specimens collected from 220 patients was simultaneously tested with the four methods. Discordant results were resolved by reviewing patients' clinical records.
Results: The prevalence of CDAD was 13.9%. Test sensitivities and specificities were 100% and 99% respectively for the cytotoxicity assay, 87.5% and 100% for ImmunoCard toxin A, 77.4% and 100% for the ToxA test and 100% and 98% for toxigenic culture.
Conclusions: The ImmunoCard Toxin A is a very rapid, individual and easy-to-perform test for the diagnosis of CDAD. It provides same-day results and may be useful for both guiding appropriate treatment and controlling nosocomial spread of C. difficile.     

Colonic histopathology in untreated celiac sprue or refractory sprue: Is it lymphocytic colitis or colonic lymphocytosis?

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.     

Identification of the membrane protein of porcine epidemic diarrhea virus

Sequence information on the genome of porcine epidemic diarrhea virus (PEDV) has only recently been determined. In contrast, very little is known about the viral proteins. In the present report we have identified the membrane glycoprotein (M) of PEDV by use of rabbit anti-peptide sera and transient expression of the cloned M gene in Vero cells and by expression in the baculovirus system. The native M protein of PEDV is incorporated into virions, is N-glycosylated, and migrates with a relative mobility (Mr) of 27 k in polyacrylamide gels. In contrast, the M protein synthesized by recombinant baculoviruses migrates with a Mr of 23 k, that is, with identical mobility as the deglycosylated product of PEDV. Thus, it appears that M protein specified by the recombinant baculovirus is poorly, if at all, glycosylated. Using monoclonal antibodies and rabbit antipeptide sera specific for the N and C termini of the M protein, we were able to show that a 19 k band detected in PEDV-infected cells but not in virions represented a fragment of M from which the C terminus had been cleaved off. Finally, by electron microscopy and immunogold labelling, the relative orientation of M within the virion envelope was determined as NexoCcyt. In conclusion, all of these data strongly support the hypothesis that PEDV should be classified with the group I coronaviruses.     

2019年广东省部分地区感染性腹泻病原学及人轮状病毒分子流行病学特征

目的 对感染性腹泻样本进行检测鉴定,并对轮状病毒A组进行病毒分离,研究2019年广东省部分地区感染性腹泻病原学及轮状病毒分子流行病学特征。方法 2019年1月1日至2020年1月12日,采集广东省广州市、东莞市和江门市临床感染性腹泻患者粪便样本,进行多重RT-PCR扩增和微球杂交技术检测鉴定,并对轮状病毒A组阳性样本进行分离后,采用半巢式PCR试验对阳性细胞培养物进行G/P基因分型。结果 共纳入706例合格病例,病原体总检出率43.06%,病毒检出率18.13%高于细菌检出率8.36%高于寄生虫检出率1.27%。病毒病原谱以轮状病毒A组G9P[8]和诺如病毒GII型感染为主,细菌病原谱以沙门菌和艰难梭菌为主,寄生虫以蓝氏贾第鞭毛虫为首。不同季度、不同年龄组病原谱构成各不相同。轮状病毒A组主要受累群体为≤5岁儿童,主要时间分布于1—4月,基因型呈现多样性,包括G2P[4]、G3P[8]和G9P[8]。结论 2019年广东省部分地区感染性腹泻病毒类病原体高于细菌类高于寄生虫类,轮状病毒A组G9P[8]、诺如GII型、沙门菌和蓝氏贾第鞭毛虫是最主要的病原体,且G9P[8]型A组轮状病毒毒株在轮状病毒感染中占主导趋势。在防控病毒性和细菌性腹泻的同时,应警惕寄生虫所致腹泻并重视混合感染的病原学监测。