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Biomedical subjects

A Morelli

Publications and source records attributed to A Morelli.

At least 145 records · Page 8Linked to original sources

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohn's disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohn's disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohn's disease and in those with colonic involvement. This may have therapeutic implications.

Adult↗

Upper gastrointestinal motor abnormalities in children with active celiac disease.

Although from the clinical point of view a GI motor disorder can be suspected in celiac disease, objective evidence for this is still lacking. We therefore conducted a study on children with active celiac disease to detect possible GI motor abnormalities in this disease. Fourteen children (age range, 1-13 years) were studied; they underwent fasting and fed manometric recordings in the gastroduodenojejunal area. Four patients were restudied after a 6-month gluten-free diet. Data were compared with those obtained in eight control children. As compared with controls, celiac disease patients showed a shorter duration of activity fronts (p < 0.01) and a significant (p < 0.01) reduction of the postprandial antral motility index; furthermore, > 90% of the patients displayed marked fasting and/or fed motor abnormalities, suggesting a neuropathic disorder. Interestingly, gut dysmotilities disappeared in the four subjects reassessed after the gluten-free diet. It is concluded that celiac disease frequently affects the motor behavior of the gut and that its effects may be reversed by appropriate diet.

Adolescent↗

Oesophageal motility in adult coeliac disease.

Coeliac sprue is a relatively frequent disease with protean clinical manifestations. Recent studies suggest that gastrointestinal motor abnormalities may explain some symptoms complained of by such patients. We investigated whether coeliac patients have oesophageal motor abnormalities from both a clinical and a physiological point of view. Thirty-six consecutive adult sprue subjects (14 during the florid phase and 22 on gluten-free diet) were studied. A clinical questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal origin) was administered. Moreover, 18 patients (13 on free and five on gluten-free diet) gave their consent for oesophageal manometry and eight subjects for pH-metry also. Oesophageal clinical symptoms were compared with those of 144 age- and sex-matched controls from a general population sample, and manometry with that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls). Manometric examination showed motor abnormalities in 67% of the subjects examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal sphincter associated with simultaneous contractions, and frequent repetitive (> 3 peaks) contractions. These abnormalities were equally distributed among free and gluten-free diet patients. pH-metry showed only one pathological reflux out of eight subjects studied. We conclude that patients with coeliac sprue may display abnormal oesophageal motility. This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease.

Adult↗

Cognitive event-related potential in hepatic encephalopathy.

A study of auditory P300 was performed on 24 patients with cirrhosis of the liver: 13 patients with hepatic encephalopathy (HE grade 1-2) and 11 patients without clinical encephalopathy (HE grade 0). The patients were also assessed using spontaneous EEG and neuropsychological methods: Mini Mental State, Digit Span and Number Connection Test. The P3 latency was found to be significantly increased in all patients (100%) with HE grade 1-2 and in 6 patients (54.5%) with HE grade 0. The clinical value of using the P300 latency in the hepatic encephalopathy is subsequently discussed.

Aged↗

Effect of NSAIDs on pepsinogen secretion and calcium mobilization in isolated chief cells.

Acid and pepsin are thought to play an important role in the process of gastrointestinal side effects induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs increase basal gastric acid secretion, the effect they exert on pepsinogen secretion is unknown. Because pepsin plays a key role in many acid-related diseases, we investigated whether NSAIDs directly stimulate pepsinogen secretion from isolated chief cells. Exposure of guinea pig gastric chief cells to indomethacin (10 microM) did not reduce cell viability as evaluated by lactate dehydrogenase and 51Cr release and trypan blue incorporation. Indomethacin (10 microM) caused two- to threefold increases in pepsinogen secretion and intracellular calcium concentrations ([Ca2+]i). Both effects were concentration dependent. Removal of extracellular Ca2+ or pretreatment of the cells with 0.5 mM lanthanum blocked both pepsinogen secretion and the [Ca2+]i increase in chief cells stimulated with 10 microM indomethacin. Exposure of isolated chief cells to indomethacin caused a 90% inhibition of prostaglandin (PG) E2 generation, but a 12-fold increase in leukotriene (LT) B4 release. Incubating chief cells with exogenously added LTB4, LTC4, LTD4, and LTE4 provoked a concentration-dependent stimulation of pepsinogen release (mean effective concentration of 0.05-0.1 nM). Maximally effective concentrations of all LTs (10 microM) increased [Ca2+]i two- to threefold. Pretreating the cells with a 5-lipoxygenase inhibitor abolished LTB4 generation induced by Ca2+ ionophore and indomethacin and reduced indomethacin-induced pepsinogen secretion 20%. In conclusion, indomethacin induced a concentration-dependent stimulation of pepsinogen secretion and [Ca2+]i in isolated chief cells. Indomethacin inhibits PGE2 generation, but increases LTB4 release. This "lipoxygenase shunt" may contribute to the effect indomethacin exerts on isolated chief cells.

Animals↗

Severity scores in respiratory intensive care: APACHE II predicted mortality better than SAPS II.

BACKGROUND: In recent years several scoring systems have been developed to describe the severity of illness, to establish the individual prognosis, and to group adult ICU patients by predicted risk of mortality. In addition, these scores can be used to measure and/or compare the quality of care in different ICUs. We compared the mortality predictions of the Acute Physiology and Chronic Health Evaluation (APACHE II) score and a new Simplified Acute Physiology Score (SAPS II) in patients with respiratory disease who require intensive care. PATIENTS & METHODS: We prospectively studied all 306 admissions from January 1, 1992 through December 31, 1994. McNemar and Hosmer-Lemeshow tests, and receiver operating characteristic (ROC) curves were used to describe and analyze our data. RESULTS: The average APACHE II score was 17.5 (SD 6.0), corresponding to a mean predicted death rate of 24.9% (SD 17.2%) as compared to an observed overall RICU mortality rate of 21.6%. The average SAPS II score was 39.1 (SD 11.1) corresponding to a mean predicted death rate of 26.0% (SD 18.4%). The ratio between the actual and predicted hospital mortality was 86% for APACHE II and 83% for SAPS II. Survivors had a significantly lower predicted risk of death than nonsurvivors (p < 0.0001) with both indices, and a higher Glasgow coma scale score (p < 0.0001). The ROC-curve analysis suggested the superior predictive ability of APACHE II in our patients. Area under the APACHE II ROC curve was 80.88% (standard error [SE] 2.89%), significantly larger (p < 0.01) than that found for SAPS II (73.52%, SE 3.61%). CONCLUSIONS: The APACHE II score was a good predictor of hospital outcome and better than SAPS II in our population.

APACHE↗

[The usefulness of transesophageal echocardiography in the follow-up of patients operated on for replacement of the ascending aorta with a tubular-valvular prosthesis (Cabrol's intervention)].

OBJECTIVES: The usefulness of transesophageal echocardiography (TEE) in assessing the postoperative results of aortic root replacement (Cabrol's procedure) was evaluated. METHODS: Between 1986 and 1993, 31 patients underwent replacement of the aortic valve and ascending aorta by a composite graft using the Cabrol procedure. Twenty-six patients had annuloaortic ectasia, two type I DeBakey dissection and four type II dissection. Hospital mortality was 9.7%. Studies were performed in 18 patients, two to 70 months (mean 27.5 months) after composite graft replacement. The following features were examined: prosthetic aortic valve function, coronary graft morphology and function, tubular graft and aneurysm wrapped around morphology and dimensions, presence of intimal flap, false lumen and thrombus in the false lumen and persistence of right atrial fistula. RESULTS: Periprosthetic leakage with significant regurgitation was detected by TEE in 3 (16.6%) of 18 patients. In one patient with infected aortic graft a fistula between the periprosthetic space and the right ventricle was detected (confirmed at reoperation). In another patient occlusion of the graft for left coronary artery was noted. In three patients (16.6%) an aneurysm of the periprosthetic space with perivalvular leakage and persistence of the fistula with the right atrium was visualized. In the two patients operated for DeBakey type I dissection an intimal flap persisted distal to the graft and in one patient flow was detected in the false lumen, while it was totally obliterated in the other. CONCLUSIONS: 1) Complications after Cabrol's procedure are not infrequent; although the real importance of some of them (periprosthetic aneurysm, persistence of dissection) is uncertain, a careful follow-up may be essential to improve the long term survival. 2) TEE is a useful and well-tolerated procedure for postoperative follow-up of patients who underwent aortic root replacement with Cabrol's procedure.

Adult↗

Adult Hirschsprung's disease mimicking Crohn's disease.

Although Hirschsprung's disease is diagnosed most commonly during infancy and childhood, some cases are seen in adults, when clinical features are usually similar to those described in younger patients. We report a case whose unusual clinical presentation led to an initial diagnosis and subsequent treatment of colonic Crohn's disease. The correct diagnosis was made only after motility measurements suggested the possibility of adult Hirschsprung's disease and prompted the histological examination of the myoenteric plexus, which led to the establishment of the correct diagnosis.

Adult↗

Circadian variations in gastric acid and pepsin secretion and intragastric bile acid in patients with reflux esophagitis and in healthy controls.

OBJECTIVES: Duodenogastric reflux is a physiological phenomenon in both fasting and postprandial state. Because this suggests that bile acids may reflux into the esophagus together with the acid in patients with reflux esophagitis, we investigated the circadian variations of acid and pepsin secretion and intragastric bile acid concentrations in 25 patients with reflux esophagitis and in 15 healthy controls. METHODS: Between-meal, nocturnal gastric and meal-stimulated acid and pepsin secretion and bile acid concentrations were measured by continuous gastric aspiration and intragastric titration. RESULTS: Bile acids were found in 85 and 59% of gastric samples (p < 0.05). Intragastric bile acid concentrations were 6-8-fold higher in esophagitis patients than controls during the day. Approximately 10% of gastric samples from reflux esophagitis patients had a pH greater than 7, and all contained more than 500 mumol/L bile acids. Bile acids and pepsin were simultaneously revealed in 98% of the gastric samples from patients with reflux esophagitis with pH less than 4. Mean daily acid output (meal excluded) averaged 3.5 +/- 0.1 in healthy subjects and 2.7 +/- 0.2 mmol/30 minutes in esophagitis patients (p < 0.05); meal-induced acid secretions were similar. Total (24-h) acid secretion averaged 192.3 +/- 12.4 and 162.4 +/- 10.5 mmol/24 h (p < 0.05). There were no differences in the daily pepsin output. CONCLUSIONS: Our data indicate that almost all "acid" gastroesophageal refluxes should be considered as "mixed" refluxes. Because bile acids are found in the stomach irrespective of whether the environment was acid or alkaline, pH-metry provides no useful information on the pattern of duodenogastric reflux into the esophagus. Variability in the composition of the gastro-esophageal refluxate may explain why the severity of esophageal lesions differs in patients with similar pattern of acid refluxes.

Adult↗

Characterization of Ca(2+)-ATPase in rod outer segment disk membranes.

The Ca(2+)-pump isolated in rod outer segment disk membranes as aspartylphosphate intermediate E-P has been characterized: the 100 kDa phosphoprotein was completely inhibited by thapsigargin, was not sensitive to digestion by calpain, and displayed a tryptic digestion pattern with the formation of two autophosphorylatable fragments of about 55 and 35 kDa. These results are typical of the calcium pumps of sarcoplasmic or endoplasmic reticulum calcium and differ from those of plasma membrane, such as the Ca(2+)-ATPase of the red blood cells, here shown as controls. The physiological role of calcium pump in disk membranes of vertebrate photoreceptors is discussed in terms of intracellular calcium buffering.

Animals↗

Hepatitis B virus antigens in peripheral blood mononuclear cells during the course of viral infection.

We studied the expression of surface (HBsAg) and core (HBcAg) proteins of hepatitis B virus (HBV) on the surface of peripheral blood mononuclear cells (PBMC) from HBV-infected patients. A total of 122 patients with different liver viral diseases was analyzed by indirect immunofluorescence with monoclonal antibodies. The 35 patients with HBV chronic active hepatitis (CAH) and 38 of 60 patients with acute hepatitis B (63%) expressed HBsAg on the PBMC. No expression was detected on the cells from both normal and HBV-unrelated viral hepatitis control groups. Serial follow-up of patients with acute hepatitis B showed that HBsAg expression by PBMC tended to be undetectable 4 months after the onset of the disease and at the same time the clinical improvement was evident. Cell cultures of EBV-transformed B lymphocytes were established from PBMC of HBV-infected patients; immunoelectron microscopy demonstrated the HBsAg on the cellular membrane. One-third of HBV-infected patients who were studied showed the expression of HBcAg by PBMC. HBcAg was detected in patients with acute hepatitis B at the early stage of infection. The cells of these patients also expressed HBsAg in PBMC. In CAH patients, a positive association was observed between the expression of HBcAg and the presence of serum HBeAg.

Acute Disease↗

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Aminopeptidases↗

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↗

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↗

Distension-stimulated propagated contractions in human colon.

To investigate the mechanisms for elicitation of peristaltic activity in the human colon, we studied the effect of balloon distension of the transverse, descending, and sigmoid colon and the rectum. Fifteen healthy subjects were studied by means of a colonoscopically positioned probe carrying a 5-cm latex balloon. After positioning of the probe, stepwise distension was performed for each colonic segment (transverse, descending, sigmoid, rectum), and the onset of large (> 50 mm Hg) and small (< 50 mm Hg) propagated waves was observed. Analysis of the tracings showed: (1) In 8/15 subjects (53.3%), balloon distension elicited propagated contractions, but these contractions were qualitatively different from the spontaneously occurring high-amplitude propagated contractions previously found to occur in association with defecation. Therefore, intraluminal distension is probably not the cause of defecation-associated high-amplitude propagated contractions. (2) Pain reports were poorly correlated with propagated contractions elicited by balloon distension, suggesting that these contractions are not the cause of the pain produced by balloon distension. (3) The transverse colon shows lower pressures, fewer pain reports, and fewer large propagated contractions in response to balloon distension as compared to the descending and the sigmoid colon.

Adult↗

Calcium pump in the disk membranes isolated from bovine retinal rod outer segments.

The existence of a Ca2+ pump in rod outer segment disks of bovine retina is strongly suggested by the isolation on sodium dodecyl sulfate polyacrylamide gel electrophoresis of a hydroxylamine-sensitive phosphorylated intermediate (E-P) of molecular mass of about 100 kDa as well as by measurements of active calcium transport and adenosine 5'-triphosphate (ATP) hydrolysis. Active Ca2+ uptake by disks was dependent on the presence of Mg(2+)-ATP, was inhibited by vanadate or lanthanum and appeared poorly sensitive to calmodulin. ATP hydrolysis by disk membranes was a function of free Ca2+ concentration in the absence of exogenous Mg2+. The presence of a Ca2+ pump on disk membranes is discussed in terms of its possible role in Ca2+ ion buffering during photoreceptor cell functioning.

Adenosine Triphosphate↗

Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha.

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.

6-Ketoprostaglandin F1 alpha↗