bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term efficacy of bismuth carbomer enemas in patients with treatment‐resistant chronic pouchitis
Authors: GIONCHETTI P. , RIZZELLO F. , VENTURI A. , FERRETTI M. , BRIGNOLA C. , PERUZZO S. , BELLOLI C. , POGGIOLI G. , MIGLIOLI M. , CAMPIERI M. 
Published: November 2003

Background: Mucosal inflammation of the ileal pouch (pouchitis) is the major long‐term complication after ileal pouch‐anal anastomosis for ulcerative colitis. Broad‐spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment‐resistant disease. Aim: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment‐resistant chronic pouchitis. Methods: Twelve patients with treatment‐resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. Results: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9–15) to 6 (4–15) (P < 0.002), and were continued on bismuth carbomer enemas administered every third night for 12 months. Patients were monitored clinically, sigmoidoscopically and histologically every 2 months for evidence of recurrence (increase ≥ 2 in the clinical symptom portion of the PDAI). Six of 10 patients (60%) were able to maintain remission throughout the 12‐month trial; 4/10 had an exacerbation, two of which occurred soon after discontinuing daily treatment. Serum bismuth levels were negligible in all patients and no side‐effects were registered. Conclusions: Our findings suggest that bismuth carbomer enemas are safe and effective in achieving and maintaining remission in patients with treatment‐resistant chronic pouchitis.
Gastric corpus IL‐8 concentration and neutrophil infiltration in duodenal ulcer patients
Authors: UEMURA N. , OOMOTO Y. , MUKAI T. , OKAMOTO S. , YAMAGUCHI S. , MASHIBA H. , TANIYAMA K. , SASAKI N. , SUMII K. , HARUMA K. , KAJIYAMA D 
Published: November 2003

Background: The purpose of the present study was to examine the association between interleukin‐8 (IL‐8) in the gastric body due to Helicobacter pylori infection and histological gastritis, as well as elucidating the effect of acid secretion inhibitors on H. pylori associated body gastritis in duodenal ulcer patients. Methods: Twenty H. pylori‐negative patients, 20 H. pylori‐positive patients with chronic gastritis without peptic ulceration, and 20 H. pylori‐positive duodenal ulcer patients (DU) were studied. Four biopsy samples were taken, each from the greater curvature of the antrum and body of the stomach. Biopsies were histologically investigated by ELISA to determine the density of H. pylori, the degree of neutrophil infiltration and the IL‐8 concentration in the mucosa. Results: In the gastric mucosa of H. pylori‐negative subjects, no IL‐8 and hardly any neutrophil infiltration were observed. In contrast, enhanced IL‐8 production and increased neutrophil infiltration were present in those infected with H. pylori. In H. pylori‐positive patients, a significant correlation was observed between the IL‐8 concentration and the degree of neutrophil infiltration, but no correlation was found in the body mucosa of those with DU. Twelve of 20 DU patients demonstrated hardly any neutrophil infiltration, despite the increased mucosal IL‐8 content in the body. The administration of omeprazole in DU patients markedly increased mucosal neutrophil infiltration even though it did not cause any significant change in the H. pylori density and IL‐8 concentration in the body. Although the effect of omeprazole was transient, a significant increase in neutrophil infiltration continued in comparison with the status before omeprazole administration in those subsequently undergoing maintenance treatment with H2‐blockers. Conclusion: In H. pylori‐positive chronic gastritis, IL‐8 concentration is enhanced in the mucosa of the body, and is associated with increased neutrophil infiltration. However, in DU patients, despite increases in body IL‐8 concentration, neutrophil infiltration is reduced and the gastritis may be localized in the antrum.
The effect of a single rectal dose of cisapride on delayed gastric emptying
Authors: BRUMMER R.‐J. M. , SCHOENMAKERS E. A. J. M. , KEMERINK† G. J. , HEIDENDAL† G. A. K. , SANDERS‡ D. G. M. , STOCKBRÜGGER R. W. 
Published: November 2003

Background: Cisapride has an established prokinetic effect in patients with delayed gastric emptying. However, rectal administration of the drug might be preferred in patients with either dysphagia or nausea due to gastroparesis. Aim: To determine the effect of a single rectal dose of cisapride 60 mg on gastric emptying in patients with delayed gastric emptying. Methods: Thirty‐two patients (16 males, 16 females) with demonstrated delayed gastric emptying received a single dose of two suppositories containing either cisapride (2 × 30 mg) or placebo, according to a double‐blind randomized crossover design. Three hours after administration of the suppositories, the patients received a radio‐labelled test meal and radio‐opaque markers for measurement of gastric emptying. Results: The mean t½ after cisapride administration (76 min, 95% CI: 68–95) was significantly shorter (P = 0.005; n = 28, per‐protocol analysis) than after placebo administration (104 min, 81–126). Four hours after ingestion of the meal significantly fewer radio‐opaque markers remained in the stomach after cisapride than after placebo administration (P < 0.05). Mild to moderate adverse events, mainly involving the gastrointestinal tract, were reported in 10 patients (31%) after cisapride treatment and in four patients (13%) after placebo (N.S.; n = 32). Conclusion: A single suppository dose of cisapride 60 mg significantly accelerates gastric emptying of the solid phase of a meal and of radio‐opaque markers in patients with previously demonstrated delayed gastric emptying.
Fistula response to methotrexate in Crohn's disease: a case series
Authors: Mahadevan U. , Marion J. F. , Present D. H. 
Published: November 2003

SummaryBackground : Controlled trials have demonstrated the efficacy of methotrexate in the induction and maintenance of remission in luminal Crohn's disease; however, its effect on fistulizing disease is unknown.Aim : To describe the response to methotrexate therapy in a series of patients with fistulizing Crohn's disease.Methods : A retrospective chart review was conducted of all patients with Crohn's disease receiving methotrexate in one practice. The response of patients with fistulizing and luminal disease was assessed using clinical and laboratory criteria. Fistula response was categorized as either complete or partial closure.Results : Thirty‐seven courses of methotrexate therapy were given to 33 patients with luminal and/or fistulizing Crohn's disease. In 16 patients with fistulas, four (25%) had complete closure, five (31%) had partial closure and all had failed or were intolerant to 6‐mercaptopurine therapy. Overall, response to methotrexate was seen in 23 of 37 (62%) treatment courses in patients with luminal and/or fistulizing Crohn's disease. Two of the 33 patients (6%) had a significant adverse event.Conclusions : In this case series, 56% of patients with Crohn's fistulas on methotrexate showed a complete or partial response to therapy. Further studies are needed to confirm the role of methotrexate alone, and in combination with other therapies, for the treatment of fistulizing Crohn's disease.
Thrombin‐mediated activation of endogenous factor XI in plasma in the presence of physiological glycosaminoglycans occurs only with high concentrations of thrombin
Authors: Wuillemin Walter A. , Mertens Koen , Ten Cate Hugo , Hack C. Erik 
Published: November 2003

The variable bleeding tendency associated with a genetic deficiency of factor XI (FXI) and the lack of bleeding disorders in individuals with a genetic deficiency of factor XII (FXII) suggest an alternative mechanism for FXI activation in vivo. Recently, thrombin has been shown to activate FXI. However, in plasma this activation has been shown to occur only with exogenous FXI and a non‐physiological cofactor (sulphatides), and the occurrence of this reaction in a plasma environment has been questioned.Using recently developed sensitive assays for FXIa–inhibitor complexes we found thrombin‐mediated and FXII‐independent activation of endogenous FXI in plasma in the presence of heparan sulphate, heparin, dermatan sulphate or dextran sulphate. Using heparan sulphate, which is present in the human vascular system, activation of about 1–2% of plasma FXI was observed, however, only after addition of very high amounts (500 nmol/l) of human α‐thrombin to FXII‐deficient plasma (at a 1 to 4 final dilution).We conclude that endogenous FXI in plasma can be activated by thrombin in the presence of various glycosaminoglycans, including the physiological compounds heparan sulphate and dermatan sulphate, but only at very high concentrations of thrombin, corresponding to 100% prothrombin activation in undiluted plasma.
Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation
Authors: Xu D. , Knaust E. , Pisa P. , Palucka K. , Lundeberg J. , Areström I. , Peterson C. , Gruber A. 
Published: November 2003

Multidrug resistance gene (mdr1) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance‐associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence‐activated cell sorter (FACS). From each cell population the 20–25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. The cell fraction with low DNR content had higher (3.8–40 times) mdr1 mRNA levels in 10/10 patients and higher (1.4–26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation.In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro
Acute myeloid and T‐cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRδ gene rearrangements
Authors: Schmidt C. A. , Przybylski G. , Tietze A. , Oettle H. , Siegert W. , Ludwig W. D. 
Published: November 2003

TCRδ gene recombination patterns were analysed by Southern blot, polymerase chain reaction and nucleotide sequencing in acute myeloid leukaemias with coexpression of lymphoid antigens (Ly+ AML, n = 10) as well as in early T‐cell acute lymphoblastic leukaemias with (My+ T‐ALL, n = 10) and without coexpression of myeloid antigens (My− T‐ALL, n = 9). These 29 acute leukaemias exhibiting TCRδ gene rearrangements were selected from 66 Ly+ AML, 14 My+ T‐ ALL and 12 My− T‐ALL cases.Similar recombination patterns, namely Dδ2Jδ1 and Vδ1Jδ1 gene rearrangements, were observed in Ly+ AML and My+ T‐ALL. In contrast to Vδ2Dδ3 rearrangements in B‐cell precursor ALL, these rearrangements require activation of a T‐cell‐specific TCRδ enhancer. Comparison of My+ T‐ALL and Ly+ AML with My− T‐ALL exhibited a higher incidence of incomplete Dδ2Jδ1 rearrangements in My+ T‐ALL and Ly+ AML. Since a Dδ2Jδ1 rearrangement is an early event in TCRδ recombination, these leukaemias seem to be arrested at an earlier stage of differentiation. Similar patterns of TCRδ rearrangements in My+ T‐ALL and Ly+ AML suggest existence of a common myeloid/T‐lymphoid progenitor cell.Although weak or missing expression of terminal deoxynucleotidyl transferase (TδT) was found in 7/10 Ly+ AML cases, no difference was observed in numbers of N‐nucleotides inserted in junctional regions when comparing with 3/10 cases exhibiting TdT expression. Since TdT activity is necessary for N‐nucleotide addition, this finding suggests down‐regulation of TδT expression after rearrangement took place in these Ly+ AML cases.
Karyotype conversion in two patients with chronic myeloid leukaemia after busulphan‐induced marrow hypoplasia
Authors: Xue Yongquan , Zhou Jin , Yu Fei , Gu Jianming , Guo Yu , Xie Xing , Lin Baojue 
Published: November 2003

We report two patients with chronic myeloid leukaemia (CML) developing hypoplasia and karyotype conversion after conventional busulphan therapy. Initially, the percentage of Ph‐positive metaphases in marrow for both patients was 100%, which steadily diminished up to a complete disappearance in case 1 and decreased dramatically in case 2 following hypoplasia. Thereafter Southern blot and RT‐PCR assays revealed no abnormalities. Both patients have survived 9 years and remained in good clinical and haematological remission without any treatment until recently.We believe that the high sensitivity to busulphan therapy resulted in hypoplasia and karyotype conversion, which contributed to prolonged survival.
Long‐term follow‐up of de novo myelodysplastic syndromes treated with intensive chemotherapy: incidence of long‐term survivors and outcome of partial responders
Authors: Wattel Eric , De Botton Stéphane , Laï Jean Luc , Preudhomme Claude , Lepelley Pascale , Bauters Francis , Fenaux Pierre 
Published: November 2003

The percentage of long‐term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known.Between 1981 and 1996 we treated 99 patients with de novo MDS who had high‐risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy.After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant).Of the 71 patients treated before 1993, with sufficient follow‐up, 10 (14%) had survived > 4 years (long‐term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49–78 months. Long‐term survivors were characterized by a significantly higher incidence of RAEB‐T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB‐T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years.Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long‐term survivors remains low, however, and is almost restricted to patients with RAEB‐T at diagnosis and no unfavourable karyotype.
Addition of granulocyte colony‐stimulating factor to chemotherapy in patients with AIDS‐related lymphoma: effects on neutrophil Fcγ receptor expression and soluble FcγRIII plasma levels
Authors: Kersten M. J. , De Jong S. , Evers L. M. , Koene H. R. , Van Oers M. H. J. 
Published: November 2003

AIDS‐related neutropenia and neutrophil dysfunction can (partly) be reversed by granulocyte‐colony stimulating factor (G‐CSF). We studied the effect of G‐CSF on neutrophil increment and levels of soluble Fcγ receptor type III in 15 patients with AIDS‐related lymphoma (ARL) undergoing chemotherapy. In six of these patients we performed a detailed kinetic analysis of the membrane expression of the functionally important Fcγ‐receptors type I, II and III. In all these patients G‐CSF induced FcγRI positive neutrophils with a decreased expression of the FcγRIII receptor. These changes were similar to those seen both in healthy volunteers and in non‐HIV‐infected individuals treated with chemotherapy. Interestingly, the mean neutrophil and sFcγRIII increment were significantly lower and more patients had a nadir granulocyte count < 0.5 × 109/l after the first cycle than after the second cycle of chemotherapy. This may be related to a therapy‐associated decrease in HIV‐1 viral load.The conclusion is that patients treated with chemotherapy for ARL have a qualitatively normal response to G‐CSF.
ALL R‐87 protocol in the treatment of children with acute lymphoblastic leukaemia in early bone marrow relapse
Authors: Giona Fiorina , Testi Anna Maria , Rondelli Roberto , Amadori Sergio , Arcese William , Meloni Giovanna , Moleti Maria Luisa , Ceci Adriana , Pillon Marta , Madon Enrico , Comis Margherita , Pession Andrea , Mandelli Franco 
Published: November 2003

Seventy‐three children with acute lymphoblastic leukaemia (ALL) in first bone marrow (BM) relapse, occurring within 30 months from complete remission (CR), were enrolled in an Italian cooperative study (ALL R‐87 protocol). This treatment programme consisted of an induction phase with intermediate‐dose cytarabine (IDARA‐C) plus idarubicin (IDA) and prednisone (PDN), followed by a multidrug consolidation therapy and bone marrow transplant (BMT). 55/73 children achieved CR (75.3%); 15 (20.5%) failed to respond and three (4.2%) died during induction. The response rate was significantly higher for children with a first CR duration 12 months (P = 0.0005) and for those with a white blood cell (WBC) count at relapse <20 × 109/l (P=0.004). The estimated disease‐free survival (DFS ± SE) at 82 months was 0.18 ± 0.05 for all responders, and 0.70 ± 0.14 for allotransplanted patients versus 0.05 ± 0.05 for those autografted (P = 0.001). The estimated probabilities of survival ± SE and event‐free survival (EFS ± SE) at 83 months were 0.16 ± 0.07 and 0.13 ± 0.04, respectively, for all enrolled children. Univariate analysis showed that age <10 years at initial diagnosis and B‐lineage immunophenotype favourably influenced both DFS (P = 0.001) and EFS probabilities (P = 0.0014 and P = 0.012, respectively), whereas a first CR duration 12 months and a WBC count at relapse <20 × 109/l were associated only with a better EFS rate (P = 0.026 and P = 0.004, respectively).Our results show the efficacy of the IDA plus IDARA‐C schedule used in the ALL R‐87 protocol in high‐risk relapsed ALL children. Allogeneic BMT proved effective for patients with an HLA sibling donor. In a multivariate analysis, age 10 years at initial diagnosis (P = 0.016) and WBC count at relapse 20 × 109/l (P = 0.048) were independently associated with a worse disease outcome.
Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo
Authors: Schreiber M , Muüller H , Wachsmuth C , Laue T , Hufert F T , Van Laer M D , Schmitz H 
Published: November 2003

Abstract
This study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV− donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4+ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.
Protection against anti-glomerular basement membrane (GBM)-mediated nephritis in C3- and C4-deficient mice
Authors: SHEERIN N S , SPRINGALL T , CARROLL M C , HARTLEY B , SACKS S H 
Published: November 2003

SUMMARY
Mice rendered completely deficient of the complement components C3 or C4 were used to determine the influence of complement activation in the heterologous phase of the anti-GBM disease model. In wild-type animals the disease is characterized by a neutrophil infiltrate, capillary thrombosis, proteinuria and C3 and C4 deposited within the glomerulus. The early infiltration of neutrophils into the glomeruli is greater in wild-type mice (2·8 ± 0·3) compared with C3-deficient (1·4 ± 0·2) and C4-deficient (1·2 ± 0·003) mice. Deficiency also protects against the subsequent development of proteinuria (2·99 ± 1·11 mg/24 h, 0·059 mg/24 h and 0·327 ± 0·14 mg/24 h in wild-type, C3-deficient and C4-deficient mice, respectively) and decreases glomerular capillary thrombosis in both C3- and C4-deficient mice. The degree of protection is greater in the C3-deficient than the C4-deficient animals, suggesting both classical and alternative pathway involvement. These studies support a critical role for complement in the development of anti-GBM disease. However, the protective effect of complement deficiency can be broken if the dose of nephritogenic antibody is increased.
B cells and monocytes are not developmentally affected in a case of reticular dysgenesis
Authors: DE LA CALLE-MARTÍN O , BADELL I , GARCÍA A , GELPÍ C , CASAMITJANA N , ESTELLA J , RODRÍGUEZ-SÁNCHEZ J L 
Published: November 2003

SUMMARY
We report a patient with reticular dysgenesis (RD) who received an HLA-identical marrow graft and remained free of infection in spite of incomplete haematological recovery. Mixed chimerism was achieved and resulted from the presence of autologous B cells and monocytes and grafting of donor T cells. Granulocyte recovery was impaired. The B cells were CD5+ (B1 cells) and appeared to be functional, since serum immunoglobulin levels became normal after the graft. The findings described here suggest that in some cases the defect selectively affects different cell types, including the more abundant leucocyte populations, granulocytes and T lymphocytes. However, B cells and monocytes appear to be relatively spared in this case of RD. Furthermore, the present case may provide insight into the mechanism involved in the expansion of distinct B cell subpopulations (B1 and B2 cells).