Autonomic cardiovascular regulation in quiescent ulcerative colitis and Crohn's disease.

BACKGROUND: In inflammatory bowel diseases, changes in autonomic enteric regulation may also affect neural cardiovascular control. However, while cardiac autonomic modulation has been shown to be impaired in active ulcerative colitis, the occurrence of cardiovascular autonomic alterations, also in the quiescent phase of inflammatory bowel diseases, is still a matter of debate. The aim of our study was thus to explore the features of cardiovascular autonomic regulation in ulcerative colitis and Crohn's disease during their remission phase. MATERIALS AND METHODS: Autonomic cardiovascular control was evaluated by time- and frequency-domain indexes of spontaneous heart rate and blood pressure variability and by assessing the baroreflex heart rate control (sequence technique) in 26 patients with ulcerative colitis, in 26 patients with Crohn's disease and in 23 healthy controls. RESULTS: The groups were matched for age, gender and body mass index. They had similar blood pressure mean levels and variability. By contrast, mean heart rate, its overall variability (standard deviation), and baroreflex sensitivity were lower in ulcerative colitis patients than in controls. Moreover, all indexes related to cardiac vagal control were significantly lower in ulcerative colitis patients with respect not only to controls but also to Crohn's disease patients. CONCLUSIONS: Cardiac vagal control is impaired in quiescent ulcerative colitis only, and not in Crohn's disease, while in both bowel diseases vascular control appears preserved. Since cardiovagal modulation seems related to anti-inflammatory mechanisms, the reduced parasympathetic cardiac regulation in apparently quiescent ulcerative colitis suggests that such systemic derangement is accompanied by local subclinical inflammations, even in the absence of clinically active inflammatory processes.

Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacterpylori antibodies in the management of dyspeptic patients in primary care.

BACKGROUND: Several tests have been proposed for evaluating dyspeptic symptoms and their relationship to the underlying gastric disease. Serum pepsinogens and gastrin-17 are known to be useful biomarkers for the detection of gastric pathologies. AIM: To evaluate the capability of screening dyspeptic patients in the primary care by analyses of serum pepsinogens I (sPGI) and II (sPGII), gastrin-17 (sG-17) and the IgG anti-Helicobacter pylori antibodies (IgG-Hp). PATIENTS AND METHODS: Three hundred and sixty-two consecutive patients with dyspeptic symptoms (208 females, mean age 50.6 +/- 16 years, range 18-88 years) referred by general practitioners for upper gastrointestinal endoscopy were enrolled. A blood sample was taken from each subject for IgG-Hp, sPGI, sPGII and sG-17 analyses. RESULTS: Two hundred and eighty-seven patients had a complete screening; of these, 132 resulted positive for Hp infection. Patients with atrophic chronic gastritis showed significantly lower serum pepsinogen I levels and sPGI/sPGII ratio than patients with non-atrophic chronic gastritis. Moreover, by calculating the values of sPGI by sG-17 and sG-17 by sPGII/sPGI, subjects with atrophic chronic gastritis could be distinguished from those with non-atrophic chronic gastritis and from those with normal mucosa, respectively. sG-17 levels were found to be a useful biomarker for the detection of antral atrophic gastritis, while the combination of sPGI, the sPGI/sPGII ratio and sG-17 was found effective in identifying corpus atrophy. CONCLUSION: A panel composed of PGI, PGII, G-17 and IgG-Hp could be used as a first approach in the 'test and scope' and/or 'test and treat' strategy in the primary care management of dyspeptic patients.

Use of bovine lactoferrin for Helicobacter pylori eradication.

BACKGROUND: One-week triple therapy is the most frequently recommended treatment for Helicobacter pylori infection. Eradication rate is satisfactory, nevertheless is advisable to look for more effective therapies. AIM: To test the efficacy of a standard triple therapy plus bovine lactoferrin in the eradication of H. pylori infection. PATIENTS AND METHODS: One hundred and fifty consecutive H. pylori positive patients, suffering from dyspeptic symptoms were recruited in a 7-day triple therapy open randomised single centre study with rabeprazole, clarithromycin, tinidazole, bovine lactoferrin (group A) or rabeprazole, clarithromycin, tinidazole (group B), or a 10-day therapy with rabeprazole, clarithromycin, tinidazole (group C). H. pylori status was assessed 8 weeks after the end of the treatment by means of a 13C-urea breath test or a H. pylori stool antigen-test. RESULTS: Eradication rates (intention to treat/per protocol) were: group A (92.2/95.9%), group B (71.2/72.5%) and group C (70.2/75%). The efficacy of triple therapy added with lactoferrin was significantly higher than other two regimens (p=0.01, intention to treat analysis; p=0.005, per protocol analysis). CONCLUSION: These results suggest that lactoferrin tested in the present study was effective in curing H. pylori and could be a new agent to assist the antimicrobials in the eradication of the bacterium.

'Serological biopsy' in first-degree relatives of patients with gastric cancer affected by Helicobacter pylori infection.

BACKGROUND: Relatives of patients with gastric cancer are at increased risk of developing this disease, especially if they are infected by Helicobacter pylori. Moreover, H. pylori-related atrophic gastritis and hypochlorhydria are well-documented risk factors for noncardia gastric cancer. Serum pepsinogen I (sPGI) and II (sPGII) levels are low in this condition. The aim of our study was to assess by means of a 'Gastropanel' blood test, including sPGI, sPGII, gastrin-17 (G-17) and antibodies anti-H. pylori (IgG-Hp). both functional and morphological features of gastric mucosa in Hp + ve subjects with a family history of gastric cancer. MATERIALS AND METHODS: Twenty-five Hp + ve subjects consecutively referred to our department for gastrointestinal complaints, selected as first-degree relatives of patients suffering from gastric cancer, were enrolled in the study and then matched for sex and age with 25 dyspeptic and Hp + ve subjects with no family history of gastric neoplasia. Blood samples were taken for determination of gastropanel in all patients; in addition, antibodies against CagA were analysed. RESULTS: No statistically significant differences were detected between the two groups as regards alcohol consumption, coffee intake and smoking habits. Mean sPGI levels in Group A (83.4 +/- 58.4 microg/L) were significantly lower than those in Group B (sPGI 159.5 +/- 80.6 microg/L; P < 0.0001) as well as sPGII (12.5 microg/L = 6.24 versus 20.6 +/- 58 microg/L; P < 0.006). No statistical difference was found between the two groups in relation to G-17 levels, IgG-Hp titres and antibodies against CagA. CONCLUSION: First-degree relatives of patients with noncardia gastric cancer affected by H. pylori infection present lower sPGI and sPGII levels, possibly due to the increased frequency of atrophic lesions in these patients.

[Laparoscopic fundoplication in gastroesophageal reflux disease: reflexions on a personal caseload]. / Fundoplicatio laparoscopica per malattia da reflusso gastroesofagea (MRGE): riflessioni su una casistica personale.

Ninety-two patients with severe, proton-pump-inhibitor-dependent gastro-oesophageal reflux disease were submitted to surgery and operated on by the same surgeon (SC) over the past 7 years (mean age: 42; range: 23-74 years). Partial fundoplication was performed in 14 patients with impaired oesophageal motility, while 78 total fundoplications were done in the others, 51 without, and 27 with division of the short gastric vessels. The mean follow-up was 29.5 months (range: 1-85 months). Conversion to open surgery was necessary in 6 patients (all in the first 40 cases). Perforation of the gastric fundus and early migration of the stomach into the mediastinum were the two most important complications observed. The mortality was nil. 39% of the patients complained of postoperative dysphagia but only five required endoscopic (4) or surgical (1) treatment. The percentages of dysphagia after partial fundoplication and total fundoplication with or without division of the short gastric vessels were 28%, 37% and 47%, respectively. In 83.7% the patients were satisfied with the clinical results and in 84% of cases medical treatment was avoided after surgery. On the basis of these data, laparoscopic surgery appears to be a good option for gastro-oeophageal reflux disease in selected patients with a poor response to, or dependent on medical treatment. However, the results of surgery may be subject to the limitations of a learning curve, as in all complex laparoscopic procedures.

Coding region intron/exon organization, alternative splicing, and X-chromosome inactivation of the KRAB/FPB-domain-containing human zinc finger gene ZNF41.

ZNF41 belongs to a cluster of human zinc finger genes residing within a gene-rich region at Xp11.23. ZNF41 encodes a KRAB/FPB (Krüppel-associated/finger preceding box) domain, a potent transcription repression motif present in hundreds of vertebrate zinc finger protein genes, composed of two protein modules, A and B. Three introns, placed at identical positions in paralogous genes, interrupt four exons encoding the ZNF41 N-terminal amino acids, the KRAB/FPB-A and KRAB/FPB-B modules, and the remaining coding region adjoined to the C-terminal zinc finger domain. Since the KRAB/FPB-A and KRAB/FPB-B modules are encoded by dedicated exons in ZNF41 and paralogous genes, exon skipping may lead to differential usage of these modules in alternative gene products. RT-PCR analysis of ZNF41 mRNAs showed that, while skipping of the KRAB/FPB-A and/or KRAB/FPB-B exons was not detected, the use of alternative donor/acceptor sites upstream of the KRAB/FPB-A exon generates multiple ZNF41 transcripts potentially encoding polypeptides differing in the N-terminal region and expressed in different tissues. The expression pattern in cell hybrids containing either active or inactive X chromosomes indicates that ZNF41, which resides within a region of the X chromosome that includes genes that are both subject to and escape X-inactivation, is susceptible to X-chromosome inactivation.

Routine intravenous cholangiography, selective ERCP, and endoscopic treatment of bile duct stones before laparoscopic cholecystectomy.

BACKGROUND: No procedure has yet been identified as the standard for the detection and management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy. METHODS: A prospective study involved 1305 patients undergoing elective laparoscopic cholecystectomy. Intravenous cholangiography was performed on all patients except those with jaundice or cholangitis, acute pancreatitis, or allergy to contrast material. Patients underwent endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy when there was a strong suspicion of choledocholithiasis, positive or inconclusive findings on intravenous cholangiography or allergy to contrast material with signs of possible choledocholithiasis. Intraoperative cholangiography was performed when patients did not undergo ERC or intravenous cholangiography and whenever the surgeon was in doubt about biliary anatomy or biliary clearance. RESULTS: Two hundred thirty-one patients (17.7%) were referred for preoperative ERC; 14 of them were referred for open surgery because of failure of ERC or sphincterotomy. Only 54 patients underwent intraoperative cholangiography. Bile duct stones, detected in 186 cases (14.2%) (68 of which were asymptomatic), were removed before surgery in 162 cases (87.1%) and during surgery in 20 (10.7%). Self-limited pancreatitis occurred in 3.6% of the patients after sphincterotomy. Laparoscopic cholecystectomy was performed in 98.7% of the cases. The conversion rate was 8% if sphincterotomy had been performed previously, and 3% after standard laparoscopic cholecystectomy (p < 0.001). The morbidity rate was 5% and the mortality rate 0.08%. During the follow-up period 4 patients had retained stones that were treated endoscopically. CONCLUSIONS: Preoperative ERC followed by laparoscopy is the best approach to treatment of patients with cholecystolithiasis and suspected choledocholithiasis.

Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial.

BACKGROUND & AIMS: The efficacy of 5-aminosalicylic acid (mesalamine) in the treatment of flare-ups of Crohn's disease is controversial. In previous studies, different locations and pathological behavior of Crohn's disease could have obscured the efficacy of these drugs that deliver their substance in different intestinal sites. The present study tested two different mesalamine formulations with 6-methylprednisolone in mild to moderate active Crohn's ileitis. METHODS: Ninety-four patients with Crohn's ileitis (Crohn's Disease Activity Index [CDAI], 180-350) were randomly assigned to receive for 12 weeks mesalamine tablets, 4 g (35 patients); mesalamine microgranular preparation, 4 g (28 patients); and 6-methylprednisolone, 40 mg (31 patients). Mesalamine microgranular preparation was a gelatin capsule containing 400 mg of mesalamine microgranules coated with Eudragit S, which has been shown to deliver the drug in the terminal ileum. RESULTS: Patients taking mesalamine tablets experienced a decrease of CDAI median score value of 113.5 (95% confidence interval [CI], 33-149) compared with 123 (95% CI, 77-155) in the mesalamine microgranular group and 154 (95% CI, 99-197) in the 6-methylprednisolone group (P = 0.07 [NS]). Remission at the final visit occurred in 19 of 31 (61%) patients taking steroids compared with 21 of 35 (60%) patients taking mesalamine tablets and 22 of 28 (79%) patients taking microgranular mesalamine (NS). Five patients on steroids were withdrawn because of side effects, and a case of pancreatitis was related to microgranular mesalamine. CONCLUSIONS: Mesalamine in microgranular formulation seems to be equally as effective as a standard dosage of steroids in the treatment of the mild to moderate form of Crohn's ileitis.

Enhanced glutathione levels and oxidoresistance mediated by increased glucose-6-phosphate dehydrogenase expression.

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway that is responsible for the generation of NADPH, which is required in many detoxifying reactions. We have recently demonstrated that G6PD expression is induced by a variety of chemical agents acting at different steps in the biochemical pathway controlling the intracellular redox status. Although we obtained evidence that the oxidative stress-mediated enhancement of G6PD expression is a general phenomenon, the functional significance of such G6PD induction after oxidant insult is still poorly understood. In this report, we used a GSH-depleting drug that determines a marked decrease in the intracellular pool of reduced glutathione and a gradual but notable increase in G6PD expression. Both effects are seen soon after drug addition. Once G6PD activity has reached the maximum, the GSH pool is restored. We suggest and also provide the first direct evidence that G6PD induction serves to maintain and regenerate the intracellular GSH pool. We used HeLa cell clones stably transfected with the human G6PD gene that display higher G6PD activity than the parent HeLa cells. Although the activities of glutathione peroxidase, glutathione reductase, and catalase were comparable in all strains, the concentrations of GSH were significantly higher in G6PD-overexpressing clones. A direct consequence of GSH increase in these cells is a decreased reactive oxygen species production, which makes these cells less sensitive to the oxidative burst produced by external stimuli. Indeed, all clones that constitutively overexpress G6PD exhibited strong protection against oxidants-mediated cell killing. We also observe that NF-kappaB activation, in response to tumor necrosis factor-alpha treatment, is strongly reduced in human HeLa cells overexpressing G6PD.

A novel X-linked member of the human zinc finger protein gene family: isolation, mapping, and expression.

We report the partial characterization of a novel putative zinc finger gene of the Krüppel-type (ZNF81), isolated from an X Chromosome (Chr) specific library. The pattern of segregation in human-hamster somatic cell hybrids of sequences homologous to the ZNF81 finger domain has established that it resides within the Xp22.1-Xp11 region. ZNF81 represents yet another example, together with ZFX, ZNF41, and ZNF21, of members of the zinc finger gene family residing within the short arm of the human X Chr. Sequence analysis showed that ZNF81 may encode a polypeptide(s) containing tandem arrays of 12 canonical C2H2 zinc fingers of the Krüppel-type at the C-terminus. Northern analysis indicated that probes from the ZNF81 finger domain hybridize to polyadenylated transcripts present in several cell lines, a result that supports the hypothesis that it is an expressed, functional member of this multigene family.

Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger-Ellison syndrome during omeprazole treatment.

Development of focal gland atrophy of the oxyntic mucosa was found in two patients with the Zollinger-Ellison syndrome undergoing long-term treatment with omeprazole. The atrophic areas revealed florid proliferation of endocrine cells in the form of both intraglandular crescents and micronodular hyperplasia. This proliferation was significantly more pronounced than in the remaining non-atrophic mucosa. The possible relationship of these changes to long-standing pharmacological therapy for gastric acid suppression is discussed.

[Endoscopic palliative treatment of malignant bile duct obstruction by endoprosthesis]. / Il trattamento endoscopico palliativo delle stenosi neoplastiche delle vie biliari mediante inserzione di endoprotesi.

Endoscopic positioning of a large biliary endoprosthesis has become a well codified procedure for palliative treatment of primary or metastatic malignant bile duct obstruction. Authors' experience, regarding 47 patients treated by this technique from February 1992, is reported. Furthermore, either absolute or site-related per cent rate of successful positioning of endoprosthesis, efficacy of procedure, early and late complications and mean survival are reported. Results confirm the effectiveness of the procedure in reducing jaundice resulting from malignant bile duct obstruction and low complication rate; early detection and treatment of prosthetic obstruction with subsequent cholangitis, that is the most important factor responsible for death, depend upon close collaboration between physician and endoscopist.

[Interaction between laparoscopic surgery and operative endoscopy. Results of an experience]. / Interazione tra chirurgia laparoscopica ed endoscopia operativa. Risultati di un'esperienza.

Nowadays it is possible to treat complex biliary disease such as cholecysto-choledochal stones with mini-invasive methods. In this field, laparoscopic surgeons and gastroenterologic endoscopists can collaborate not only in the planning of endo-laparoscopic sequential treatment of biliary stones but also in the successful treatment of complex cases having either surgical or endoscopic complications. Here are presented the results which 14 months of collaboration between laparoscopists and endoscopists have brought about in the diagnostic and therapeutic fields. In particular, the results are documented of the sequential endo-laparoscopic treatment of cholecysto-choledochal calculi proposed for 39 patients, of inverse laparo-endoscopy carried out in 2 cases, and of therapeutic procedure used to treat an iatrogenic perforation of the biliary tree by mini-invasive methods. The experience reported is an example of how technological progress is gradually pushing aside the barriers still existing between medicine and surgery.

Members of the zinc finger protein gene family sharing a conserved N-terminal module.

We report the isolation of human members of a sub-family of structurally related finger protein genes. These potentially encode polypeptides containing finger motifs of the Krüppel type at the C-terminus, and a conserved amino acid module at the N-terminus; because of its invariant location the latter is referred to as finger preceding box (FPB). The FPB, detected also in previously described finger proteins from human, mouse and Xenopus, extends over approximately 65 amino acids and appears to be composed of two contiguous modules: FPB-A (residues 1-42) and FPB-B (residues 43-65). The latter is absent in some of the members analyzed. Elements A and B and the zinc finger domain are encoded by separate exons in the ZNF2 gene, a human member of this sub-family. The positioning of introns within this gene is remarkable. One intron flanks and a second interrupts the first codon of the FPB-A and FPB-B modules, respectively. A third intron occurs a few nucleotides downstream of FPB-B marking its separation from the remainder of the coding sequences. This organization, together with the absence of FPB-B in some cDNAs, supports the hypothesis that mRNAs encoding polypeptides that include one, both or none of the FPB-A and FPB-B modules may be assembled through alternative splicing pathways. Northern analyses showed that members of this sub-family are expressed as multiple transcripts in several cell lines. The sequences of distinct cDNAs homologous to the ZNF2 gene indicate that alternative splicing events adjoin either coding or non coding exons to the FPB sequences.

S-100 immunoreactive interdigitating cells in normal and in Down's syndrome human thymuses.

The present research deals with the localization of the interdigitating cells (IDCs) in normal and in Down's human thymuses. Eight thymic biopsy samples of normal children from 16 months to 10 1/2 years and six samples of Down's children from 2 months to 6 1/2 years were stained by the indirect immuno-peroxidase method using an anti-S-100 protein serum. IDCs are localized in the medullary zones, always numerous in all the Down's thymuses and in an age-related decreasing number in normal thymuses. The interrelationships between the physiological and pathological role of IDCs in inducing self-tolerance and T-cell activation and the numerical distribution in normal and in Down's human thymuses are discussed.

Malignant enterochromaffinlike cell carcinoid of the gastric stump: an ultrastructural study.

A metastasizing carcinoid of the gastric stump found 25 years after Billroth II gastric resection for duodenal ulcer is described. Electron microscopy and optical endocrine cell staining proved the tumor to be composed of enterochromaffinlike (ECL) cells. This unusual combination further shows that, at variance with most of these tumors, ECL cell carcinoids may develop also in a condition excluding a trophic effect of gastrin. This case emphasizes the malignant behavior of gastrin-independent ECL cell tumors.

Isolation and expression analysis of a human zinc finger gene (ZNF41) located on the short arm of the X chromosome.

We have isolated a novel human zinc finger gene, ZNF41, from a human X-chromosome-specific library. Nucleotide sequence analysis reveals that ZNF41 potentially encodes a polypeptide featuring an array of 18 contiguous zinc fingers of the C2H2 type. Multiple polyadenylated transcripts homologous to ZNF41 are present at different levels in several distinct cell types. Southern analyses of somatic cell hybrids containing either intact or rearranged X chromosomes confirm the genomic origin of the isolated gene and establish that it is localized between Xcen and Xp22.1.