Maria Antonietta Pelli

Mortality in patients with coeliac disease and their relatives: a cohort study

BACKGROUND Although previous studies have shown increased mortality in patients with coeliac disease and their relatives, no data are available in relation to different patterns of clinical presentation. We assessed mortality in patients with coeliac disease and their first-degree relatives. METHODS We enrolled, in a prospective cohort study, 1072 adult patients with coeliac disease consecutively diagnosed in 11 gastroenterology units between 1962 and 1994, and their 3384 first-degree relatives. We compared the number of deaths up to 1998 with expected deaths and expressed the comparison as standardised mortality ratio (SMR) and relative survival ratio. FINDINGS 53 coeliac patients died compared with 25.9 expected deaths (SMR 2.0 [95% CI 1.5-2.7]). A significant excess of mortality was evident during the first 3 years after diagnosis of coeliac disease and in patients who presented with malabsorption symptoms (2.5 [1.8-3.4]), but not in those diagnosed because of minor symptoms (1.1 [0.5-2.2]) or because of antibody screening (1.2 [0.1-7.0]). SMR increased with increasing delay in diagnosis and for patients with poor compliance with gluten-free diet. Non-Hodgkin lymphoma was the main cause of death. No excess of deaths was recorded in relatives with coeliac disease. INTERPRETATION Prompt and strict dietary treatment decreases mortality in coeliac patients. Prospective studies are needed to clarify the progression of mild or symptomless coeliac disease and its relation to intestinal lymphoma.

Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation

Idiopathic chronic constipation is a frequent and disabling symptom, but its pathophysiological grounds are still poorly understood. In particular, there is little knowledge about the relationships between distal (anorectal area) and proximal (colonic area) motor abnormalities in this condition, especially concerning high-amplitude propagated colonic activity. For this purpose, we studied 25 patients complaining of severe idiopathic constipation and categorized them as normal- or slow-transit constipation according to colonic transit time. Twenty-five age-matched controls were also studied. Investigations included standard anorectal motility testing and prolonged (24-hr) colonic motility studies. Analysis of results showed that both groups of constipated patients displayed significantly different (P<0.05) minimum relaxation volumes of the internal anal sphincter, defecatory sensation thresholds, and maximum rectal tolerable volumes with respect to controls. Patients with normal-transit constipation also showed lower internal anal sphincter pressure with respect to slow-transit constipation and controls (P<0.001 andP<0.02, respectively). The daily number of high-amplitude propagated contractions (mass movements) as well as their amplitude and duration, was significantly reduced in both subgroups of constipated patients (P<0.02 vs controls). We conclude that (1) in normal-transit constipation, motor abnormalities are not limited to the anorectal area; (2) patients with slow-transit constipation probably have a severe neuropathic rectal defect; (3) prolonged colonic motility studies may highlight further the functional abnormalities in constipated subjects; and (4) an approach taking into account proximal and distal colon motor abnormalities might be useful to understand pathophysiological grounds of chronic constipation and lead to better therapeutic approaches.

Breath alkanes determination in ulcerative colitis and Crohn's disease

PURPOSE: By considering the pathophysiologic basis of inflammatory bowel diseases, a role for excessive lipid peroxidation caused by oxygen free radical compounds has been proposed repeatedly. However, to date only a few studies are available on this topic in human beings. This study was designed to assess breath alkanes in a group of patients with active inflammatory bowel disease by a technique that clearly distinguishes pentane from isoprene, to prevent overestimation of values as in previous studies. PATIENTS: Twenty patients with a diagnosis of active inflammatory bowel disease (10 with Crohns disease and 10 with ulcerative colitis) were studied. Extension of the disease was similar between patient groups, and all were treated with equivalent doses of steroids and salicylates. METHODS: Breath alkanes determination was performed by a standard procedure involving a gas cromatography column able to separate pentane from isoprene. RESULTS: Overall, significant differences between patients with inflammatory bowel diseases and controls were found for ethane, propane, and pentane, but not for butane and isoprene. Isoprene was clearly distinguished from pentane, demonstrating that the significant elevation of pentane levels in patients with inflammatory bowel diseases is a real phenomenon and not an artifact caused by coelution with isoprene. CONCLUSIONS: An excess of lipid peroxidation is probably an important pathogenetic factor in inflammatory bowel diseases, and this may be assessed through a nonivasive method. Because this method previously also has been shown to be able to evaluate disease activity, it could be a useful tool for studying patients with inflammatory bowel diseases.

Abnormal gastrointestinal motility in patients with celiac sprue

No study to date has objectively investigated whether the motor behavior of the small bowel is abnormal in celiac sprue. The purpose of this study was to systematically address this topic by means of intraluminal pressure recordings in a series of such patients. Sixteen subjects (nine adults, seven children, age range 2–69 years) with celiac sprue were recruited and studied while untreated. Manometric examination was carried out for 6 hr during fasting and 3 hr after a meal. Adult celiac patients displayed a significantly (mean ±sem) greater frequency of migrating motor complexes in comparison to controls during fasting (4.44±1.6 vs 2.45±0.20,P<0.01), whereas no differences were found in the pediatric group with respect to this variable. Fasting motor abnormalities, chiefly represented by discrete clustered contractions, giant jejunal contractions, and bursts of nonpropagated contractions, were discovered in a high percentage in both groups of celiac subjects (89% in adults and 44% in children, respectively). Similar abnormalities were observed in the postprandial period, especially in adults. In conclusion, patients with celiac sprue frequently display discrete gastrointestinal motor abnormalities, which though perhaps nonspecific may account for several symptoms complained of by such patients.

Genotoxic effect of bile acids on human normal and tumour colon cells and protection by dietary antioxidants and butyrate

BackgroundColorectal cancer is the second cause of death for tumour worldwide. Among the risk factors for this disease the dietary habits seem to have a pivotal role. An elevated intake of fats causes a high release in the gut lumen of bile acids that are positively correlated with colorectal cancer, since they act as detergents and proliferation promoters. Recently, it was evidenced that bile acids can also be able to induce DNA damage.Aim of the studyIn this study the genotoxicity of deoxycholic acid (DCA) and chenodeoxycholic acid CDCA) has been evaluated in human normal colonocytes derived from 60 colon biopsies and in tumour cells. The involvement of reactive oxygen species (ROS) and the oxidative DNA damage was assessed. In addition, the protective effect exerted by both two well-known antioxidants commonly present in the diet, β-carotene and α-tocopherol, and butyrate which is known to be involved in the regulation of several cellular functions, has also been tested.MethodsThe DNA damage was evaluated by the “comet assay” or single cell gel electrophoresis (SCGE) both in its conventional use and by the Endonuclease III modified method, which allow to detect the presence of oxidized pyrimidines.ResultsBile acids (CDA and CDCA) resulted genotoxic on both normal and tumour human colon cells. The inclusion of the endonuclease III digestion step in the comet assay demonstrated that bile acids induced an oxidative DNA damage. In addition, treatment of colonocytes with bile acids in the presence of the antioxidants (β-carotene, α-tocopherol) and Na-butyrate caused a reduction of DNA damage.ConclusionOur results suggest that bile acids may be involved in the tumour initiation by inducing a DNA oxidative damage, and so add further evidences to the preventive properties of antioxidants present in the Mediterranean diet.

Volatile Alkanes and Increased Concentrations of Isoprene in Exhaled Air during Hemodialysis

In this study we examined breath volatile hydrocarbon concentrations in exhaled air of hemodialysis patients. We assessed both C2–C5 alkanes – among them ethane and pentane the production of which in man is essentially due to the action free radicals exert on polyunsaturated fatty acids – and isoprene, an unsaturated hydrocarbon the biosynthesis and biological effects of which are the subject of controversy and mounting interest. Twenty patients were studied. Evaluation was performed intrapatient in the breath of patients with chronic renal failure, before and after dialysis (20 patients) and, in the same cases, during hemodialytic treatment (10 patients). Breath concentrations of these volatile hydrocarbons, determined before dialysis, were not different from those of normal subjects. Dialysis did not modify the levels of the C2–C5 saturated hydrocarbons ethane, propane, butane and pentane. Instead, there was a marked increase in isoprene in all patients (basal values rose by a mean of 270%). Since isoprene was not present in the fluids or filters used for dialysis and there were only traces in the ambient air, the isoprene must have been produced endogenously during hemodialysis. As no situation has previously been reported to increase endogenous production of isoprene in humans, patients in hemodialysis offer a unique opportunity to investigate in depth the medical, biological and toxicological aspects of isoprene.

Low-amplitude propagated contractile waves: a relevant propulsive mechanism of human colon.

BACKGROUND Human colonic motility is still poorly understood, especially as far as concerns its propulsive function. Available data refer almost exclusively to the forceful propulsive activity, which is recognized as high-amplitude propagated contractions, the manometric equivalent of mass movements. By contrast, information on less vigorous propulsive contractions is still lacking. AIMS To investigate the presence and behaviour of low-amplitude propagated contractile waves (less than 50 mmHg in amplitude) in the colon of healthy humans during a 24-hour study period. SUBJECTS AND METHODS A series of 16 healthy volunteers of both sexes entered the study, and were investigated by a standard technique involving a colonoscopically-positioned manometric catheter. During the study, two standard 1,000 kcal mixed meal and a 450 kcal breakfast were served. The recordings were, therefore, scanned for the presence of low-amplitude propagated contractile waves (waves of less than 50 mmHg in amplitude, propagated over at least three consecutive recording ports), their daily distribution, and their relationship with physiological events. RESULTS Low-amplitude propagated contractile waves were constantly present in all the tracings, with an average of about 61 events/subject/day and a mean amplitude of about 20 mmHg. More than 80% of these events appeared during the day, with a significant (p<0.05) increase after meals and after morning awakening. In 25% of subjects, these waves were accompanied by emission of flatus. CONCLUSIONS In the human colon, low-amplitude propagated contractile waves are a constant physiological propulsive pattern, which is generally related to sleep-wake cycles and meal ingestion.

Intestinal pseudoobstruction secondary to hypothyroidism : importance of small bowel manometry

Surgicalypothyroidism may lead to secondary pseudoobstruction. We report a patient with intestinal symptoms, from hypothyroidism in which previous conventional examinations were negative. Gastrointestinal manometry disclosed features of pseudoobstruction, and we discuss the importance of performing functional studies in selected cases, in as much as symptoms seemed to resolve on replacement therapy.

Effect of Lansoprazole on Human Leukocyte Function

Recent findings on the capacity of omeprazole to influence various leukocyte functions, in vitro, raises the question on the potential use of protonic pump inhibitors, commonly used in the treatment of acid-secretion-related disorders, as immunomodulators. The aim of this study was to evaluate the in vitro effect of lansoprazole on human natural killer (NK) cell cytotoxix activity, chemotaxis and superoxide anion (O2*-) generation exerted by polymorphonucleated cells (PMNs). NK cytotoxicity activity was assessed by a 51Cr release assay, PMN chemotaxis was determined by an under agarose method and O2*- generation was analyzed on the basis of reduced cytochrome C. Incubation times with lansoprazole was 30 min for PMNs and 1-4.5 hours for NK cells, respectively. Lansoprazole induced significant dose dependent inhibition of NK cell activity and PMN functions at concentrations ranging from 100 to 1,000 microM. This study demonstrate that lansoprazole, like omeprazole, inhibits several leukocyte functions, in vitro, then suggesting that protonic pump inhibitors are able to provoke these effects, at least at certain doses.

Prolonged (24-Hour) Manometric Recording of Rectal Contractile Activity in Patients with Slow Transit Constipation

A periodic motor activity, named the rectal motor complex, has been recently described in the healthy human rectum. We studied the rectal contractile activity for 24 h by a low compliance manometric system in a group of 10 women with slow transit constipation. Analysis of the 24-hour manometric recordings showed that these subjects: (1) had overall scarce rectal motility; (2) display few rectal motor complexes (average, 3.3 +/- 1.3/subject/24 h) which are irregularly distributed over time, and (3) respond weakly to ingestion of a standard meal (average duration of the motor response 19 +/- 6 min). The observations suggest that an underlying neuropathic process may be involved in the pathogenesis of the impaired rectal motility in patients with slow transit constipation.