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Biomedical subjects

G Latella

Publications and source records attributed to G Latella.

At least 19 recordsLinked to original sources

Multiple organ dysfunction in ulcerative colitis.

OBJECTIVE: The mortality rate in severe ulcerative colitis (UC) is commonly attributed to major colonic complications or surgical procedures. Early recognition of the severity of the colitis, intensive medical treatment, and prompt surgery have all contributed to improving its outcome over the past 40 yr. Recently, we have observed some fatal cases of severe UC in which death was related to multiple organ dysfunction syndrome (MODS). This complication, associated with a very high mortality rate, may occur in several acute critical diseases, both infectious and noninfectious, but has so far not been reported in UC. The aim of this study was to evaluate the prevalence and outcome of MODS in severe UC. METHODS: The records of 180 consecutive patients admitted to the Gastrointestinal Unit, University of Rome for an acute severe attack of UC during the period 1976-1998 were retrospectively analyzed. Severity of UC was defined according to the criteria of Truelove and Witts. MODS was defined according to the original criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992. All patients were on a standard intensive regimen consisting of total parenteral nutrition and hydrocortisone 100 mg q.i.d. Colectomy was performed according to the timing of the Oxford intensive regimen. RESULTS: Of these 180 severe UC patients, 11 (6.1%) experienced clinical and laboratory features of MODS. The lung was involved in five patients, the kidney in three, the liver in seven, the central nervous system in three, the hematological system in three, and the pancreas in one. MODS was preceded by toxic megacolon in five patients and by so-called "impending megacolon" in four, whereas in two patients no previous complications of UC were observed. MODS developed during the first attack of colitis in seven patients and during relapse in four. The overall mortality rate was 12/180 (6.6%). Of the 12 patients who died, eight (72.7%) had MODS. CONCLUSIONS: These data indicate that UC must be included among the causes of MODS. In our referral center for inflammatory bowel diseases, MODS was responsible for the majority of UC cases with a fatal outcome. The timely identification of signs of MODS should prompt admission to an intensive care unit and emergency surgery.

Adolescent↗

Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment.

AIM: To measure mucosal concentrations of mesalazine in ulcerative colitis patients treated with oral mesalazine alone, compared to patients treated with both topical and oral mesalazine. METHODS: Twenty-two patients with mild to moderate ulcerative colitis were randomized to receive 2.4 g/day of oral mesalazine (11 patients) or 2.4 g/day oral plus 4 g/day of topical mesalazine (11 patients). After 2 weeks of treatment, endoscopic biopsies specimens were taken from the rectum and in descending colon just distal of the splenic flexure and stored to -80 degrees C for later assay (HPLC). Wilcoxon's rank sum test for unpaired data was used for the statistical analysis. RESULTS: Mucosal levels of mesalazine in the rectum were significantly higher in patients who received oral plus topical treatment than in those who had oral treatment alone (52.1 ng/mg, range: 13.6-122.1 vs. 0.2 ng/mg, range: 0.2-9.7, respectively; P < 0.0001). Similarly, in the descending colon, the mucosal concentrations of mesalazine were significantly higher in patients who had oral plus topical treatment than in those receiving oral treatment alone (46.6 ng/mg, range: 6-112.6 vs. 15.9 ng/mg, range: 2.3-42.4, respectively; P=0.01). CONCLUSIONS: Topical treatment of mesalazine significantly increases mucosal concentrations of mesalazine up to the splenic flexure, supporting the rationale to treat left-sided ulcerative colitis with topical formulations of mesalazine.

Administration, Oral↗

Carbonic anhydrase I reduction in colonic mucosa of patients with active ulcerative colitis.

Ulcerative colitis (UC) is associated with low intracolonic pH and unbalanced transmucosal ionic exchanges. Along the gastrointestinal tract carbonic anhydrase isoenzyme I (CA-I) is specifically expressed in colon epithelium and is involved in mucosal control of ion, fluid, and acid-base balance. Since altered CA-I expression may play some role in UC, CA-I was measured at the mRNA and protein level and carbonic anhydrase (CA) enzyme activity was determined in colon biopsies of 14 UC patients (6 remission, 4 mild, 4 moderate UC) and of 12 healthy subjects. Patients with mild or moderate UC showed a significant reduction of CA-I mRNA and protein and of total CA activity in the inflamed mucosa compared to controls. Patients with UC in remission showed a pattern of CA-I expression and CA activity similar to controls. This is the first report showing a reduction in the expression of CA-I in active UC.

Acute Disease↗

Acute colitis following colonoscopy.

Colitis following colonoscopy is an acute, self-limited condition characterized by tenesmus and bloody diarrhea appearing within 48 hours of colonoscopy or sigmoidoscopy. Glutaraldehyde used for disinfection of the endoscopes is considered to be the main etiological agent. Three cases of severe acute self-limited colitis are described in this report. All three were observed within one week, and showed the typical anamnestic, clinical, endoscopic, histological, and radiological features of glutaraldehyde-induced colitis. The main characteristics in these cases were the time relationship with colonoscopy and the severity of the clinical presentation, with symptoms of systemic reaction and intense and diffuse edema of the colonic mucosa. The clinical and morphological features may mimic those of colonic ischemia. All three patients recovered completely within a few days, one spontaneously and two after treatment with steroids, antibiotics, and mesalazine. Acute colitis following colonoscopy should be regarded as one of the complications related to colonoscopy, and it should be taken into account in the differential diagnosis of acute colitis.

Acute Disease↗

Characterization of the mucins produced by normal human colonocytes in primary culture.

Mature goblet cells filled with mucin ready for secretion represent about one third of the cells in primary cultures of human colonocytes. In the present study characterization of the mucins produced by cultured human colonocytes was made by histochemical methods by lectin and monoclonal antibody binding. Two monoclonal antibodies and three lectins (Dolichos biflorus (DBA), Helix pomatia (HPA) and Arachis hypogea (PNA) recognizing epitopes or sugar haptens characteristic of different stages of mucin glycoprotein maturation, were employed. The reactivity to these probes was tested both on cultured colonocytes and on tissue sections of the normal colon mucosa. The results show that the mucins produced in culture are glycosylated to the mature form, as they show the same reactivity to lectins and antibodies of the mucins expressed in tissue sections of the normal colon mucosa. In addition, it is demonstrated that cultured human colonocytes do not express mucins reactive to PNA, which are characteristic of tumors. Since the cultured colonocytes maintain the expression of differentiated functions for at least three days, they may offer a useful model to study metabolism, function and regulation of colon mucins in health and disease.

Adult↗

Human colonocytes in primary culture: a model to study epithelial growth, metabolism and differentiation.

The purpose of this work was to set up an in vitro model for the study of normal and pathological functions of the colonic epithelium. We have isolated colonic crypts by mild proteolytic digestion and mechanical dissociation of human biopsy material obtained during colonoscopy. The crypts, free of connective tissue, when placed in culture rapidly attached to the substrate and formed colonies containing over 95% of epithelial cells. Histochemical and ultrastructural characterization of the colonies showed the presence of both absorptive and secretory cells, exhibiting a high degree of differentiation. Proliferative activity occurred mostly during the first 24 h and progressively declined thereafter. The cells survived and maintained differentiated characteristics for at least three days in culture. This method can be used to study normal functions of the colonic epithelium. It may also be employed to investigate both noxious and protective factors in pathological conditions such as inflammatory bowel disease and colorectal neoplasia.

Cell Differentiation↗

Abnormalities of colonic mucin secretion and metabolic changes after internal urinary diversion for bladder exstrophy. A prospective study.

Ten patients with different types of internal urinary diversion for bladder exstrophy were studied prospectively in order to assess metabolic abnormalities and morphological, histochemical and lectin binding changes in the colorectal mucosa. The histochemical and/or lectin binding changes which were found in the majority of patients were identical to those observed in premalignant and malignant conditions of the colon. In some cases they were detectable 3 years after the initial examination but were completely absent from the colorectal mucosa of normal subjects. Metabolic disturbances (metabolic acidosis, increased anion gap, hyperchloraemia) were observed in a substantial number of asymptomatic patients. These findings stress the need for regular endoscopic, histological and metabolic follow-up in these patients and for life-long treatment with bicarbonate or citrate.

Adolescent↗

Colonoscopic control of uretero-enteric anastomoses in internal urinary diversion.

Twenty-four patients with internal urinary diversion following total bladder ablation underwent colonoscopic control of the uretero-enteric anastomoses. The techniques performed were: rectal bladder with colostomy according to Mauclaire (11 patients); rectal bladder with abdomino-perineal pull-through according to Heitz-Boyer/Hovelacque (6); ureterosigmoidostomy (7). The uretero-enteric anastomoses were divided into 3 categories according to the colonoscopic appearance: "nipple-like", nearly flat and flat anastomosis. Urographic examinations were carried out in all patients and the results demonstrated that the "nipple-like" anastomosis was the most successful for the preservation of upper urinary tract integrity.

Anastomosis, Surgical↗

Fecal lactate and ulcerative colitis.

Impaired metabolism of short-chain fatty acids, as well as a modified fecal ionogram, have been reported in ulcerative colitis. Fecal water samples from 62 patients with ulcerative colitis were analyzed in the present investigation to evaluate changes in SCFAs and lactic acid in relation to activity and severity of disease. Short-chain fatty acid levels were high in quiescent and mild disease (162.6 +/- 63.6 and 147.8 +/- 63.2 mM/L, respectively), but significantly decreased in the severe form (64.7 +/- 46.9 mM/L). Lactate showed a progressive increase from mild colitis (3.0 +/- 1.8 mM/L) to severe colitis (21.4 +/- 18.6 mM/L). It thus appears that mild colitis displayed a fecal pattern characterized by normal pH and bicarbonate, slightly impaired electrolyte handling, high short-chain fatty acid values, and only moderately increased lactate. Severe colitis, on the other hand, was characterized by low fecal pH, bicarbonate, and potassium, high sodium and chloride, low short-chain fatty acid levels, and very high lactate levels. A critical lowering of intraluminal pH, which shifts bacterial metabolism from short-chain fatty acid to lactate production, may be responsible for the intraluminal pooling of lactate.

Colitis, Ulcerative↗

Early recognition of toxic megacolon.

Increased amounts of small bowel gas are a frequent finding on plain abdominal films in toxic megacolon (TMC), but they may also be found in patients with severe colitis. We studied 69 consecutive patients with severe ulcerative colitis to evaluate whether an increased gas content of the small intestine may identify patients prone to TMC. The intestinal gas was measured on plain abdominal films by means of a planimeter. On the basis of gas values, 38 patients showed a normal and 31 an increased amount of small intestinal gas. The outcome of the disease (complications, need for surgery, and mortality rate) and 18 clinical and hematochemical findings were compared in the two groups. Of the 31 patients with increased gas, seven developed TMC, whereas this complication was not observed in the 38 patients with normal gas. The only other different features between the two groups were blood pH and base excess, which were significantly higher in the patients with increased small bowel gas content. We therefore suggest that persistent abnormal gaseous distension of the small bowel, together with severe metabolic alkalosis, characterizes a subgroup of patients with severe colitis at high risk for the development of TMC. The strict surveillance of these patients led to early recognition of seven cases of TMC and prompt institution of aggressive medical treatment. Since all these patients survived, the early detection of TMC may improve prognosis.

Adolescent↗

Seeking clues for a positive diagnosis of the irritable bowel syndrome.

Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysiological markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid-base balance, serum electrolytes and the composition of faecal water (electrolytes and organic anions), were studied in thirty-eight diarrhoeal patients out of a series of ninety-three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagnosis of the syndrome. Serum electrolytes and systemic acid-base balance were within the normal range. Faecal electrolytes were also normal (Na 26.6 +/- 19.3 SD; K 66.8 +/- 28.3; Cl 19.1 +/- 15.2 mEq 1(-1)), despite the finding of a moderately increased 24-h faecal output. The K:Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (131.4 +/- 62.6 SD vs. 108.5 +/- 58.3 mEq 1(-1). Only lactic acid concentration was significantly higher than in controls (1.3 +/- 1.2 vs. 0.5 +/- 0.2). Despite these findings it is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome.

Acid-Base Equilibrium↗