Biomedical subjects

M A Pelli

Publications and source records attributed to M A Pelli.

At least 19 recordsLinked to original sources

PubMed2001

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.

Adult↗

PubMed2001

Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity.

INTRODUCTION: Diverticular disease of the colon is one of the most common pathologic entities in western countries. Although altered motility of the large bowel is commonly believed to be one of the major pathophysiologic mechanisms, no convincing evidence has been reported yet. In fact, only a few conflicting studies concerning distal colonic motility (with no information on forceful propulsive activity) are available in the literature. PURPOSE: The purpose of the present study was to investigate basal and stimulated (postprandial) colonic motility from the transverse (not affected), descending, and sigmoid colon in patients with diverticular disease, together with detection of high-amplitude propagated contractions (mass movements). Motility data from patients were compared with those obtained in healthy control subjects. METHODS: Ten patients and 16 control subjects of both sexes were recruited for the study. In all subjects, colonic motility was recorded for a 24-hour period by a colonoscopically positioned manometric catheter. Two 1000-kcal mixed meals were served during the study. RESULTS: Compared with control subjects, patients with diverticular disease displayed significantly increased amounts of motility in the affected segments; the response to a physiologic stimulus (meal) was also abnormal in the patients' group. Diverticular disease patients also had a significant increase of forceful propulsive activity compared with control subjects (average = 10.3 +/- 2.7/subject/day high-amplitude propagated contractions for patients and 5.5 +/- 0.8/subject/day for control subjects; P = 0.051); interestingly, about 20 percent of such activity was abnormal, being propagated in a retrograde fashion. CONCLUSIONS: We concluded that patients with diverticular disease of the colon have abnormal motor and propulsive activities of the large bowel, which are confined to the affected segments.

Adult↗

PubMed2001

Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells.

Epidemiological studies support the involvement of short-chain fatty acids (SCFA) in colon physiology and the protective role of butyrate on colon carcinogenesis. Among the possible mechanisms by which butyrate may exert its anti-carcinogenicity an antioxidant activity has been recently suggested. We investigated the effects of butyrate and mixtures of SCFA (butyrate, propionate and acetate) on DNA damage induced by H(2)O(2) in isolated human colonocytes and in two human colon tumour cell lines (HT29 and HT29 19A). Human colonocytes were isolated from endoscopically obtained samples and the DNA damage was assessed by the comet assay. H(2)O(2) induced DNA damage in normal colonocytes in a dose-dependent manner which was statistically significant at concentrations over 10 microM. At 15 microM H(2)O(2) DNA damage in HT29 and HT29 19A cells was significantly lower than that observed in normal colonocytes (P < 0.01). Pre-incubation of the cells with physiological concentrations of butyrate (6.25 and 12.5 mM) reduced H(2)O(2) (15 microM) induced damage by 33 and 51% in human colonocytes, 45 and 75% in HT29 and 30 and 80% in HT29 19A, respectively. Treatment of cells with a mixture of 25 mM acetate + 10.4 mM propionate + 6.25 mM butyrate did not induce DNA damage, while a mixture of 50 mM acetate + 20.8 mM propionate + 12.5 mM butyrate was weakly genotoxic only towards normal colonocytes. However, both mixtures were able to reduce the H(2)O(2)-induced DNA damage by about 50% in all cell types. The reported protective effect of butyrate might be important in pathogenetic mechanisms mediated by reactive oxygen species, and aids understanding of the apparent protection toward colorectal cancer exerted by dietary fibres, which enhance the butyrate bioavailability in the colonic mucosa.

Biopsy↗

PubMed2001

Onset, time course, and persistence of increased haemodialysis-induced breath isoprene emission.

Recent findings of increased isoprene emission in the exhaled breath of patients undergoing haemodialysis and experimental evidence of the potential toxic and cancerogenic effects of isoprene hydrocarbon led us to assess how long haemodialysis patients are exposed to how much isoprene after a single haemodialysis session. Patients with end-stage renal failure on regular 4-hour (from 08.00 to 12.00 h) maintenance haemodialysis three times weekly were monitored. The breath isoprene content was analyzed by gas chromatography. Intrapatient evaluations were performed by collecting samples before, during, and immediately after the haemodialysis session, during the following hours, and on the following nondialysis day. The breath isoprene content increased in all patients. Isoprene overproduction showing a biphasic pattern was first detected soon after the dialysis session ended. These data show that haemodialyzed patients seem to be consistently exposed to high endogenous isoprene concentrations. The mechanisms and implications of this endogenous isoprene overproduction need to be elucidated with regard to the mevalonic pathway and in the physiopathological setting of the uraemia-dialysis syndrome.

Adult↗

PubMed2000

Double-blind manometric assessment of two topical glyceryl trinitrate formulations in patients with chronic anal fissures.

BACKGROUND: Chronic anal fissure is a frequent and troubling condition, that may need surgical sphincterotomy for relief of symptoms. However, this approach may yield minor incontinence in up to 30% of cases. Interest has, therefore, recently increased in "chemical sphincterotomy" by using topical glyceryl trinitrate ointment. Unfortunately, there is, to date, no specific pharmaceutical preparation of such compound. AIMS: To compare, according to a randomized double-blind crossover study, the effects of a pharmaceutical preparation of a specific 0.2% glyceryl trinitrate ointment (PMF 303) and of the common preparation reported in the literature on the anal resting pressure in patients with anal fissure. PATIENTS AND METHODS: Twelve patients with chronic anal fissure (6 males and 6 females, age range 23-60 years] were recruited for the study. Two paired manometric studies were carried out at one-week intervals. After the basal anal pressure had been assessed, the patients were randomized to receive either one of the two preparations, and manometric measurements were repeated at 20, 40 and 60 minutes. RESULTS: No differences were found between anal resting pressure in the basal study. Both preparations were able to significantly decrease (p=0.001) anal pressure throughout the study period. No significant differences were found between the two preparations. CONCLUSIONS: PMF 303 is able to decrease anal pressure in patients with anal fissure, to a similar extent to the widely tested (galenic) literature preparation. Availability of a specific formulation for the treatment of this condition may be clinically useful.

Administration, Topical↗

PubMed1999

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 Crohn's 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 chromatography 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 noninvasive 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.

Adolescent↗

PubMed1999

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 C(2)-C(5) 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 C(2)-C(5) 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.

Adult↗

PubMed1999

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.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Valproate-induced epileptic tonic status.

We observed a young patient with slight mental retardation, suffering from drug-resistant tonic-clonic seizures, who presented a status epilepticus (SE), in two separate periods when valproic acid (VPA) was added to the phenobarbital (PB) already being used in the patient's therapy. The VPA-induced SE was characterized by normal plasma levels of antiepileptic drugs (AEDs), normal ammonemia and normal liver function. The case we studied represents the first report on a VPA-induced SE. Furthermore the case confirms that VPA, as well as causing encephalopathy secondary to hyperammonemia, may also provoke a primary involvement of the central nervous system (CNS), specially when used in young epileptic, mentally retarded subjects. In an attempt to explain the paradoxical effect of VPA we hypothesise that the SE could be due to an increase in excitatory activity producing a consequent epileptogenic effect in those subjects with a predisposition for toxic reaction to VPA therapy due to congenital anomalies of neural networks.

Adolescent↗

PubMed1998

Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Caprilli & Gruppo Italiano Studio Colon-Retto.

BACKGROUND AND METHODS: Four hundred and eighty-four patients with inflammatory bowel disease underwent clinical examination, ultrasonography, and biochemical liver function tests, to estimate the prevalence of hepatobiliary alterations. The patient group included patients without a history of liver disease. Controls were recruited from patients with functional symptoms. RESULTS: More patients with ulcerative colitis than controls had liver steatosis and increased alkaline phosphatase levels. Factors increasing the probability of liver damage were long-standing disease, the presence of moderate/severe disease activity, and treatment with steroids and mesalazine. A significant association was found between biliary disease and long-standing colitis and also therapy with steroids and mesalazine. Alkaline phosphatase and aminotransferase levels were significantly higher in Crohn's disease patients than in controls. Hepatic and biliary damage was found more commonly in the 1st year after diagnosis. CONCLUSIONS: The monitoring of hepatobiliary function is suggested for patients with inflammatory bowel disease, even in the absence of symptoms and history.

Adolescent↗

PubMed1997

Quality control study of H2 breath testing for the diagnosis of carbohydrate malabsorption in Italy. The "Tenue Club" Group.

BACKGROUND AND AIMS: H2 breath testing is increasingly used in Italy. The aim of this multicenter study was to assess the accuracy of this technique in the diagnosis of carbohydrate malabsorption. METHODS: An anonymous questionnaire was used to collect information about H2 breath testing methods and to design the quality control study. Fifteen out of 23 laboratories responded to the questionnaire and 12/23 completed the entire study. RESULTS: The survey revealed that a large variety of H2 testing methods are employed in Italy, but none have been previously tested for accuracy. This prospective study showed that these tests fail to identify > 20% of patients with malabsorption. In contrast, a new method based on single H2 breath measurement at 6 hours after lactulose ingestion and a cutoff value of greater than 5 ppm, had a sensitivity of 92% +/- 4% and a specificity of 94% +/- 0.5%. Increasing the cut-off to 10 ppm resulted in a sensitivity of 88% +/- 9% and a specificity of 100%. This improved accuracy was obtained with a much simpler testing procedure in which only one breath sample is analyzed, in contrast to the baseline and multiple subsequent samples that are analyzed using the currently employed techniques. CONCLUSIONS: A great improvement in the accuracy of the H2 breath test, as well as a considerable saving in terms of time and costs, may be possible through the use of a new, simplified H2 breath test followed by careful H2 analysis.

Breath Tests↗

PubMed1996

Estimating the incidence of coeliac disease with capture-recapture methods within four geographic areas in Italy.

STUDY OBJECTIVE: To estimate the incidence rate of newly diagnosed cases of coeliac disease in Italy. DESIGN: This was a descriptive study of coeliac disease incidence in the period 1990-91. SETTING: During 1990-91 newly diagnosed cases of coeliac disease were signalled by several sources including diagnostic records of departments of paediatrics, general medicine and gastroenterology, national health service records for the supply of gluten free diets and the archives of the Italian Coeliac Society. PATIENTS: Altogether 1475 cases were flagged throughout Italy, 478 of whom were selected, corresponding to 270 individual patients from a target population resident in four areas: Provices of Turin and Cuneo (Piedmont Region, northern Italy); Province of Brescia (Lombardia Region, northern Italy); Umbria Region (central Italy) and Sardinia Region (insular Italy). Only for these areas were patients flagged from several sources and the reference population was identifiable. MAIN RESULTS: The overall crude incidence rates for all ages per 100,000 residents per year were 2.4, 2.7, 1.5, and 1.7 in the four areas, respectively. The childhood cumulative incidence rates (aged < or = 15 years) per 100,000 live births were 143, 141, 72, and 80 respectively. The mean ages at diagnosis were similar for both childhood and adult cases throughout the areas--these were around 4 and 34 years respectively. For each area, the incidence rate was constantly higher in the main city than elsewhere. Using the capture-recapture method, an estimated completeness of case archives of 0.84 was obtained, whereas this figure was only 0.47 for hospital sources. CONCLUSIONS: This population based study on the incidence of coeliac disease shows that several information sources should be used to avoid underestimation. The incidence rate of coeliac disease in Italy was among the highest in Europe, and was widely variable showing highest figures in Piedmont and Lombardia and the lowest in Umbria and Sardinia. This trend was not due to different age at diagnosis, which suggests variable diagnostic awareness of the disease rather than different environmental patterns affecting the clinical presentation.

Adolescent↗

PubMed1994

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 and P < 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.

Adolescent↗

PubMed1994

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.

Adult↗

PubMed1994

[Reduced ex vivo production of superoxide anion by polymorphonuclear leukocytes during therapy with omeprazole. A pharmacological effect?].

Among available drugs, omeprazole is the one that cures gastric acid secretion-related pathologies, including reflux oesophagitis which responds poorly to H2-receptor antagonists, most rapidly and efficaciously. This marked therapeutic action is thought to reflect the drug's capacity to adequately control parietal hydrochloric acid secretion. Our data suggest an omeprazole effect on human neutrophil function too. Neutrophils are more or less a constant, and often conspicuous anatomo-pathological component of the phlogistic processes associated with gastric acid secretion. A direct or indirect effect exerted by omeprazole on leukocyte function would be of great scientific-biological and therapeutic interest. Furthermore, it would contribute to marking the drug superior in terms of more rapid relief of the symptoms and range of therapeutic action.

Adult↗

PubMed1993

Hydrogen breath test and scintigraphic gastrocolic transit time in diabetics with autonomic neuropathy.

We assessed gastrocolic transit time in 10 diabetic patients with autonomic neuropathy and 10 healthy age-matched controls by measuring breath hydrogen rise and scintigraphic bolus progression after ingestion of an isosmotic lactulose solution containing 99m-Tc-diethylentriamine-pentaacetic acid. Mean transit time in diabetics with autonomic neuropathy was significantly slower with respect to controls, with a good correlation between the two techniques. Moreover, diabetics had a significantly shorter discharge time (defined as the period that elapses between the arrival of the meal into the cecum and the hydrogen increase in the expired air). It is concluded that the selective lipid malabsorption seen in diabetic patients could be the result of cecal-ileal reflux, as a contaminating consequence of the last ileal loop. A possible motor innervation defect of the ileo-cecal valve is postulated in these subjects.

Adult↗

PubMed1993

Adenocarcinoma of the duodenal bulb in a young coeliac woman.

Coeliac sprue patients display an increased frequency of malignant neoplasms of the gastrointestinal tract. These neoplasms are chiefly represented by lymphomas, occurring in patients over 50. We describe the onset of a duodenal adenocarcinoma in a young woman with coeliac disease and discuss the unusual features of this case.

Adenocarcinoma↗

PubMed1992

Oral bile acid treatment and the patient with Zellweger syndrome.

The cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down-regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2-mo-old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition.

Administration, Oral↗