The value of serologic markers in indeterminate colitis: a prospective follow-up study

BACKGROUND & AIMS: In the absence of pathognomonic markers for Crohn's disease (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease depends on a compendium of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity to the individual disorders. In 10% of cases of colitis, no differentiation can be made between CD and UC; these patients are diagnosed with indeterminate colitis (IC). We evaluated the value of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing IC. METHODS: Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up prospectively. RESULTS: A definitive diagnosis has been reached for 31 of 97 patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10 patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS: Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity.     

Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response

Background: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance.Aim: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated.Methods: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg⁻¹ day⁻¹) in a single dose at bed time (n=13) or in three divided gifts with meals (n=14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between.Results: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean±SEM) was 40.1±2.4 in the single dose group vs 40.8±2.8 in the multiple dose group (p=NS) and was positively correlated with biochemical improvement (AP: r=0.47, p=0.02; GGT: r=0.58, p=0.002; ASAT: r=0.67, p=0.002; ALAT: r=0.52, p=0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens.Conclusion: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.     

Electrogastrography in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy

BACKGROUND/AIMS: The aim of this prospective study was to characterize gastric myoelectrical activity in patients with Roux-en-Y reconstruction after previous Billroth gastrectomy. METHODOLOGY: Thirteen patients entered the study (6 men and 7 women, aged 35-57). The mean time from Roux-en-Y reconstruction to electrogastrography (EGG) recording was 5 years. Surface cutaneous EGG was recorded using a Digitrapper EGG in the morning both fasting and after a standard solid test meal. All patients assessed their dyspeptic symptoms at the time of EGG in a semi-quantitative subjective scale. RESULTS: EGG was abnormal in all studied patients (but one postprandial recording). Dyspepsia was not meal-related and was not more severe in Helicobacter pylori positive patients. There was a significant negative correlation between time from Roux-en-Y reconstruction to EGG recording and bradygastria percent activity, both fasted and postprandial (r = -0.576; p = 0.0022). There was an inverse trend between severity of dyspepsia and normal slow-wave rhythm percent activity. Older patients tended to have more severe dyspepsia. CONCLUSIONS: The results of this study suggest that abnormal EGG recording is associated with dyspepsia in patients after Roux-en-Y reconstruction.     

A novel EPAS1/HIF2A germline mutation in a congenital polycythemia with paraganglioma

Congenital polycythemias have diverse etiologies, including mutations in the hypoxia sensing pathway. These include HIF2A at exon 12, VHL gene (Chuvash polycythemia), and PHD2 mutations, which in one family was also associated with recurrent pheochromocytoma/paraganglioma (PHEO/PGL). Over the past two decades, we have studied seven unrelated patients with sporadic congenital polycythemia who subsequently developed PHEO/PGL with, until now, no discernible molecular basis. We now report a polycythemic patient with a novel germline HIF2A ^F374Y (exon 9) mutation, inherited from his mother, who developed PHEO/PGL. We show that this is a gain-of-function mutation and demonstrate no loss-of-heterozygosity or additional somatic mutation of HIF2A in the tumor, indicating HIF2A ^F374Y may be predisposing rather than causative of PHEO/PGL. This report, in view of two other concomitantly reported PHEO/PGL patients with somatic mutations of HIF2A and polycythemia, underscores the PHEO/PGL-promoting potential of mutations of HIF2A that alone are not sufficient for PHEO/PGL development.     

Limitations of peritoneal lavage with antiseptics in prevention of recurrent colorectal cancer caused by tumor-cell seeding

PURPOSE: Exfoliated or soiled free malignant cells have serious consequences in patients undergoing gastrointestinal cancer surgery. The present study evaluates the toxicity and efficacy of cytotoxic agents in the prevention of cell seeding and tumor growth in the peritoneal cavity in an experimental model. METHODS: Mtln3 adenocarcinoma cell viability was testedin vitro using the trypan blue exclusion test after incubation with povidone-iodine or chlorhexidine.In vivo, Fischer rats were inoculated with 10⁵ or 10⁶ cells followed by peritoneal lavage with physiological saline, chlorhexidine 0.02 percent, providone-iodine low molecular weight 1 percent or povidone-iodine high molecular weight 1 and 2 percent in different quantities and incubation times. RESULTS: Chlorhexidine 0.02 percent and povidone-iodine low molecular weight 1 percent or high molecular weight 2 percent, killed over 98 percent of 10⁵ or 10⁶ tumor cellsin vitro. Povidone-iodine low molecular weight 1 percent and high molecular weight 2 percent were toxic and lethal when 5 ml were applied in the peritoneal cavity three times for five minutes. Chlorhexidine 0.02 percent applied after inoculation of 10⁵ or 10⁶ cells, reduced the tumor development only to 70 and 80 percent. Application of 5 ml povidone-iodine 1 percent low molecular weightor high molecular weight, three times for one and five minutes, after inoculation of 10⁶ cells did not change the tumor take. However, inhibition of Mtln3 cells to form metastases was observed. When povidone-iodine low molecular weight 1 percent was used three times for one minute after 10⁵ tumor cells were soiled, no toxicity was observed and the tumor take was reduced to 30 percent (P<0.05). CONCLUSIONS: Povidone-iodine toxicity proved to be a major issuein vivo. However, povidone-iodine low molecular weight 1 percent was safe when used for short periods and very effective when a limited number of tumor cells was inoculated. The use of cytotoxic agents to prevent recurrent disease caused by tumor cell seeding in patients seems to make sense only when the inoculum size of exfoliated or soiled cancer cells is limited.     

呼吸前反馈调节、情景想象和过度通气

通过大量的科学证据 ,我们论述了代谢的负反馈调节不是呼吸调节的唯一机制。醒觉时呼吸的前反馈调节起了主导作用 ,前反馈调节可以在血气异常引起的负反馈调节之前 ,对将要发生的异常进行纠正 ,预见性地改变通气 ,而代谢的变化随后发生 ,避免了负反馈调节所具有的波动和滞后的缺点 ,使呼吸调节系统具有更大的灵活性和适应能力。在前反馈调节的形成过程中 ,经典的巴甫洛夫条件反射学说可能起了重要作用 .尤其重要的是表象作为条件刺激形成的条件反射 ,研究表象作为条件刺激如何形成呼吸的前反馈调节对揭示高通气综合征的发病机制具有重要意义…