Zinsmeister, Alan R.

ABSTRACTBackground:Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch‐anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch‐anal anastomosis for ulcerative colitis and familial adenomatous polyposis.Methods:Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme‐linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence.Results:The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant.Conclusions:There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch‐anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.

SummaryAt our institution, proctocolectomy with rectal mucosectomy and ileoanal anastomosis with endorectal pull‐through is now the procedure of choice for young patients with chronic ulcerative colitis and familial polyposis. We have followed up 66 patients (37 male and 29 female, with a median age of 16 years) for at least 6 months after closure of the temporary ileostomy. The patients were seen regularly in follow‐up or were sent a comprehensive questionnaire to assess their condition. Twenty‐two patients had the construction of a J‐pouch. and 44 had a straight ileo‐anal pull‐through. Stool frequency, day (median 4 to 7 stools) and night (median 1 to 3 stools), was similar in the two groups. Voluntary continence was excellent in both groups during waking hours. Occasional night‐time incontinence in small volumes, mild perianal itching, and minimal bleeding from irritation were similar in both groups. Most of the patients could distinguish gas from stool. When medication was used, bulk agents were usually chosen, with a nonspecific anti‐diarrheal agent taken occasionally. A few patients with the straight ileo‐anal pull‐through expressed some dissatisfaction early during the follow‐up period: however, all but two patients expressed satisfaction later. Of the 66 patients, 41 had at least one complication during the postoperative period; however, in 26 the complications were minor. The more severe complications included small bowel obstruction (11 patients requiring surgical decompression), infection (one patient requiring surgery), and transient neuropathy (three patients).

Serological testing for Helicobacter pylori infection is one of the diagnostic methods of choice. Various commercial kits that use different antigens have been developed, but data on their diagnostic accuracy and direct comparisons between the tests are lacking. We aimed to evaluate the sensitivity, specificity, and predictive value of three immunoglobulin G enzyme-linked immunosorbent assay kits: Pylori stat, Helico-G, and Premier H. pylori. Serum samples and gastric biopsy findings from 76 patients were evaluated. We found by using a priori cutoff values that the Pylori stat, Helico-G, and Premier kits had overall sensitivities of 96, 96, and 88%, respectively, and specificities of 94, 86, and 96%, respectively, compared with gastric biopsy findings. For 232 serum samples, the Pylori stat test and a previously validated standard serological assay on which the test was based disagreed in 3% of the cases, while for 76 samples that were tested, Helico-G and a previously validated standard assay on which it was based disagreed in 8% of the cases. The intra- and interassay precision of each of the test kits was high. We conclude that serology based on any of these commercial tests represents a reliable and valid method for the diagnosis of H. pylori whether or not highly purified antigens are used.

Enzyme-linked immunosorbent assays (ELISAs) have been developed to diagnose Helicobacter pylori infection. However, the methods are not standardized. We therefore prospectively evaluated the sensitivities and specificities of ELISAs developed in the United States and the United Kingdom in a study population comprising 41 consecutive symptomatic outpatients and 35 volunteers. At endoscopy, multiple biopsies were obtained for histology and culture and stained sections were graded for chronic gastritis, active chronic gastritis, and density of H. pylori. Serum samples were analyzed for H. pylori by ELISA. The first set of assays for immunoglobulin G (IgG) and IgA used a pool of sonicated isolates of H. pylori from five patients in the United States (antigen A). The second set of assays, developed in the United Kingdom, used three different antigens: antigen 1, an acid-extractable surface antigen; antigen 2, an acid-extractable antigen from an aflagellate variant; and antigen 3, a urease-containing fraction. Cutoff scores for positive results were determined a priori on the basis of previous serological studies. There was close agreement between histology and culture. In the study population, 36% of the individuals were H. pylori positive. The diagnostic value of the different ELISAs were highly comparable, and the crude antigens performed as well as the more purified antigens. The antigen A IgG had a sensitivity and specificity of 96 and 94%, respectively; the values for antigen 1 were 93 and 96%, respectively. The antigen A IgA and antigen 3 assays were the least sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

Abstract Using a highly sensitive fluorescence in situ hybridization method with probes for BCR and ABL1 (D-FISH), we studied 37 paired sets of bone marrow and blood specimens, collected within 24 to 96 hours of each other, from 10 patients before and during treatment for chronic myeloid leukemia (CML). The normal range for 500 interphase nuclei was ≤4 (≤0.8%) nuclei based on 10 bone marrow and 10 blood specimens from normal individuals. The percentage of neoplastic nuclei was usually lower in blood than bone marrow. However, changes in the percentage of neoplastic nuclei in blood and bone marrow tracked closely over the course of therapy and with the results of quantitative cytogenetic studies on bone marrow. This result indicates that D-FISH is useful to test blood from patients with CML to monitor therapy. Moreover, by analysis of 6,000 nuclei with D-FISH, residual disease was identified in bone marrow and blood for patients in complete cytogenetic remission. Consequently, D-FISH analyses of interphase nuclei from blood could substitute for Q-cytogenetic studies on bone marrow. Thus, it may not be necessary to collect bone marrow samples so frequently to monitor therapy in CML.

Using a highly sensitive fluorescence in situ hybridization method with probes for BCR and ABL1 (D-FISH), we studied 37 paired sets of bone marrow and blood specimens, collected within 24 to 96 hours of each other, from 10 patients before and during treatment for chronic myeloid leukemia (CML). The normal range for 500 interphase nuclei was ≤4 (≤0.8%) nuclei based on 10 bone marrow and 10 blood specimens from normal individuals. The percentage of neoplastic nuclei was usually lower in blood than bone marrow. However, changes in the percentage of neoplastic nuclei in blood and bone marrow tracked closely over the course of therapy and with the results of quantitative cytogenetic studies on bone marrow. This result indicates that D-FISH is useful to test blood from patients with CML to monitor therapy. Moreover, by analysis of 6,000 nuclei with D-FISH, residual disease was identified in bone marrow and blood for patients in complete cytogenetic remission. Consequently, D-FISH analyses of interphase nuclei from blood could substitute for Q-cytogenetic studies on bone marrow. Thus, it may not be necessary to collect bone marrow samples so frequently to monitor therapy in CML.

We investigated a new method using fluorescence in situ hybridization and DNA probes that span the common breakpoints of t(9;22)(q34;q11.2) and that detect double BCR/ABL fusion (D-FISH) in bone marrow cells with this translocation, one on the abnormal chromosome 9 and one on the Philadelphia chromosome (Ph chromosome). D-FISH patterns were abnormal in 30 of 30 specimens with classic, simple, complex, and masked Ph chromosomes. Based on 200 nuclei from each of 30 normal specimens, the mean percentage of false-positive cells was 0.25 ± 0.39. Thirty-seven specimens from 10 patients were studied before treatment and two or more times at 4-month intervals after treatment with interferon-α2b (IFN-α2b) with or without ara-C. Based on 200 nuclei, the results of D-FISH in these specimens correlated closely with quantitative cytogenetics and accurately quantified disease within a few percent. We studied 6,000 nuclei for each of six specimens, three normal and three from patients with chronic myeloid leukemia (CML) in cytogenetic remission. The normal cutoff for 6,000 nuclei was 0.079% and patients in cytogenetic remission had residual disease ranging from 7 (0.117%) to 53 (0.883%) Ph-positive nuclei. We conclude that D-FISH can detect the Ph chromosome and its variant translocations and accurately quantify disease in CML at diagnosis and at all times after treatment, including cytogenetic remission.

AbstractBackgroundNon‐ulcer dyspepsia (NUD) is a heterogeneous disorder, which is characterized by upper gastrointestinal symptoms and sensorimotor disturbances, including abnormal gastric emptying (GE) and increased intestinal chemosensitivity, and associated with greater plasma glucagon‐like peptide‐1 (GLP‐1) levels during duodenal lipid infusion. However, the relationship(s) between these disturbances and daily symptoms in NUD is variable. We hypothesize that abnormal GE and symptoms during a GE study and during duodenal lipid infusion are associated with the severity of daily symptoms and that GLP‐1 mediates symptoms during duodenal lipid infusion in NUD.MethodsGastric emptying of solids, symptoms during the GE study and duodenal lipid infusion, and daily gastrointestinal symptoms (2 week diary) were measured in 24 healthy controls and 40 NUD patients. During duodenal lipid infusion, participants received the GLP‐1 antagonist exendin 9‐39 or placebo.Key ResultsIn controls and patients, GE of solids was normal in 75% and 75%, delayed in 8% and 12.5%, or rapid in 17% and 12.5%, respectively. No controls but 26 patients (65%) had severe symptoms during the GE study. During lipid infusion, gastrointestinal symptoms were greater (P = .001) in patients and not affected by exendin. Symptoms during GE study and lipid infusion accounted for respectively 62% and 37% of variance in daily symptom severity.ConclusionsIn NUD, symptoms during a GE study and to a lesser extent during lipid infusion explain the variance in daily symptoms. Intestinal chemosensitivity is not reduced by GLP‐1 antagonist. Assessment of symptoms during a GE study may provide a useful biomarker for NUD in research and clinical practice.

Summary Background Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking. Aim To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients. Methods A double‐blind, placebo‐controlled trial was performed. Adults meeting IBS Rome III criteria with ≥3 pain attacks per month were randomised to pregabalin 225 mg vs placebo twice daily for 12 weeks. Questionnaires were completed weekly. The primary endpoint was average pain Bowel Symptom Scale (BSS) scores weeks 9‐12. An intention‐to‐treat analysis of covariance evaluated treatment effects on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi‐squared test. Results Eighty‐five patients were recruited and randomised. Sample characteristics include: mean age 39.4 (SD = 14.6); 73 (86%) female; 37 (44%) IBS‐D, 29 (35%) IBS‐M, 18 (21%) IBS‐C. The pregabalin arm had lower average pain‐BSS scores weeks 9‐12 (25 vs 42, P = 0.008). Compared with placebo, the overall IBS BSS severity score was lower in the pregabalin arm (26 vs 42, P = 0.009). Differences were observed for the diarrhoea‐BSS and bloating‐BSS scores ( P = 0.049 and 0.016, respectively). No differences between groups were seen for constipation‐BSS scores. Adequate relief was not different between the two arms (46% vs 36%, P = 0.35). 63% pregabalin vs 45% placebo had a change in pain score ≥30 at week 12 from baseline ( P = 0.10). Post‐treatment IBS‐QoL scores did not differ between groups. Conclusion This trial suggests that pregabalin may be beneficial for IBS abdominal pain, bloating and diarrhoea.