[Ulcerative colitis: the ultrastructural and differential diagnostic aspects].
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Biomedical subjects
Publications and source records attributed to E Trabucchi.
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The effect of perioperative intraperitoneal (ip) (2 mg/kg) vs intravenous (iv) (1.5 mg/kg) mitomycin-C on healing of intestinal anastomoses was studied in rats after jejunal section and anastomosis. When the animals were killed 7 days after surgery 52.8% in the ip group had an anastomotic leak (41.2% causing death of the animals), compared to 20% in the iv group and none in the control group. Mean anastomotic bursting pressure was 156 mm Hg in the ip group, 178 mm Hg in the iv group, and 203 mm Hg in controls (P less than 0.01). Hydroxyproline content of the intestinal segment containing the anastomosis was 2.26 micrograms/mg in the ip group, 3.49 in the iv, and 4.91 in controls (ip vs controls, P less than 0.01). Histological examination of the anastomoses in rats given ip mitomycin showed significantly "slower" anastomotic healing than in iv rats and controls. Electron microscopy showed that the mean diameter of collagen fibers was significantly smaller (P less than 0.05) in ip rats (34 nm) than iv (51 nm) and controls (79 nm). An intraoperative bolus of mitomycin thus significantly impaired the healing of a jejunal anastomosis in the rat, more so after ip than iv injection. Thus in clinical practice ip adjuvant chemotherapy after surgery should perhaps be delayed until wound repair has reached an advanced stage.
This study was performed to see whether or not protection of the endothelial cells contributes to the antithrombotic effects of heparin. New Zealand albino rabbits were subjected to jugular vein stasis by single caudal ligation for 2 h. Three treatments were given: saline (control group), heparin (0.2 mg/kg) 5 or 45 min before ligature of the vein. Groups of 6-8 animals were killed at 0, 5, 15, 30 and 120 min. The following parameters were determined: (1) involution and damage of the endothelial cells by scanning and transmission electron microscopy; (2) incidence and weight of thrombi in the lumens of the veins after 2 h stasis, and (3) effects of heparin on APTT and anti-Xa activity. In the control group, stasis caused a considerable involution of the endothelial cells in the first 30 min, followed by fibrin deposition and thrombus generation. Heparin strongly reduced the damage to the endothelial cells, with very evident protection of the cell membranes, and prevented thrombus generation: there were significant decreases in both incidence and weight of thrombi. These effects of heparin were evident both shortly after (maximal anticoagulant effect) and long after (no anticoagulant effect) pretreatment. We think that, under the experimental conditions we used, heparin prevented venous thrombosis at least partially by protection of the endothelial cells, through unknown mechanisms.
Prokinetic drugs are commonly used for treatment of reflux oesophagitis. Although much data has been collected in clinical trials, their therapeutic effects are still uncertain. In this study the effects of L-sulpiride, if any, were examined when used to treat reflux oesophagitis in thirty patients. The patients were divided into two groups: a control group and a group given 25 mg t.i.v./day, p.o. of L-sulpiride for 30 days. They were treated as outpatients and had endoscopic, histological and ultrastructural examinations on the 30th and 60th days of treatment. It was found that the symptoms of patients with reflux oesophagitis were alleviated and the endoscopic and ultrastructural lesions of patients with minor oesophagitis were also decreased. In other patients, symptoms improved without resolution of the lesions. The authors conclude, therefore, that L-sulpiride would be appropriate treatment for Grade I cases.
The effectiveness of intravesical administration of bacillus Calmette-Guerin as a prophylaxis of superficial bladder cancer has been definitely demonstrated. On the other hand, therapeutic regimens, duration effects, efficacy of either maintenance cycles or repeated courses of therapy in case of failures are still controversial. We report the results achieved in 15 cases of carcinoma in situ of the bladder and in 48 cases of superficial bladder cancer (Ta-T1 stage of disease) with bacillus Calmette-Guerin immunotherapy. Our patients underwent an initial six week cycle and a following maintenance cycle with monthly administrations for one year. Median follow-up was 19 months (range 18-21 months). Patients with carcinoma in situ are now free of disease; on the contrary, patients with Ta-T1 tumors experienced 18 recurrences (28%). There was a marked decrease of recurrence rate when compared to previous local chemotherapy. We report in detail the adverse effects encountered and both histologic and ultrastructural findings observed after immunotherapy. Bacillus Calmette-Guerin therapy can influence positively the natural history of the disease but possible adverse effects should always be considered before starting the treatment.
Oxygen free-radicals are known to impair wound healing after ischaemia-reperfusion or polymorphonuclear cell stimulation. Furthermore, they reduce the breaking strength of all recent wounds and might be a cause of wound leakage. This study was performed to evaluate whether or not hyaluronic acid can reduce the risk of wound impairment caused by free-radicals, in rats with abdominal sepsis, polymorphonuclear cell stimulation or cytochrome C function derangement produced by xenobiotics. Male Sprague-Dawley rats with open wounds received phenazine methosulfate or zimosan, or had abdominal sepsis to induce oxygen free-radical generation. There were three groups of treatment: hyaluronic acid cream, hyaluronic acid ethyl ester gel, and placebo. The reduction in wound size was measured from the 1st to the 11th postoperative day; biopsies were taken for histological evaluation. Every other day, a gentle debridement was performed in all the groups of animals. We found that hyaluronic acid and its ethyl ester derivative significantly improved the wound healing of rats subjected to an increased generation of oxygen free-radicals. It remains to be established whether or not hyaluronic acid acts as a scavenger of free-radicals.
This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage.
To study whether or not the autonomic nervous system influences the defense mechanisms of the gastric mucosa, groups of Sprague-Dawley rats were given stimulants and inhibitors of the different components of the vagus and celiac nerves before administration of absolute or 70% w/v ethanol. The effects of vagotomy and sympathectomy on "adaptive cytoprotection" were studied, as were the effects of blocking the muscarinic receptors and stimulation of beta-adrenergic receptors. We found that: (1) cholinomimetic agents and norepinephrine make the damage caused by 70% ethanol worse; (2) atropine is the only agent that fully protects against absolute ethanol; (3) vagotomy and sympathectomy abolish the effects of atropine and adaptive cytoprotection; and (4) beta-adrenergic stimulation replaces conditions that allow adaptive cytoprotection and the protection by anticholinergics. These results suggest that two different reflexes are triggered by ethanol: when low concentrations are given, the beta-adrenergic-mediated effect is prevalent, with protection of the mucosa; when high concentrations are given, the cholinergic-mediated effect is prevalent with damage of the mucosa.
Biopsy material taken from kidneys of 14 patients with renal stones before performing extracorporeal shock wave lithotripsy (ESWL) and an average of 15 days after was examined histologically and ultrastructurally. In the post-ESWL specimens, light microscopy revealed edema and extravasation of urine and blood into the interstitial spaces, blocking of cortical tubules by hemorrhagic streaks and widespread dilatation of the veins, with signs of endothelial destruction and partial organization of thrombi. By using the electron microscope, abnormalities of the endothelium and glomerular epithelium, hemosiderin accumulations in the tubular cells and small linear patches of fibrosis at the corticomedullary junction and in the cortical interstitial spaces were seen. This preliminary report indicates that renal damage can be shown soon after ESWL on histological and ultrastructural studies and that the lesions observed can be either reversible or permanent.
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Mast cells are known to participate in three phases of wound healing: the inflammatory reaction, angiogenesis and extracellular-matrix reabsorption. The inflammatory reaction is mediated by released histamine and arachidonic acid metabolites. Compound 48/80 and disodium-cromoglycate are both able to increase skin breaking strength shortly after wounding. Under light and electron microscopy we found that small, granule-poor, irregular mast cells (MLMC) accumulate in the wound. This suggests that the small MLMC (mucosal-like mast cells) migrate into the skin during wound healing, and that both CTMC (connective-tissue mast cells) and MLMC are involved in tissue repair. Moreover, there is some evidence that mast cells participate in angiogenesis, since heparin is able to stimulate endothelial-cell migration and proliferation in vitro, and protamine to inhibit these processes and also angiogenesis in vivo. When the effect of protamine on wound breaking strength was examined, we encountered a decrease which was not prevented by heparin administration. Further studies are needed to demonstrate that protamine is specifically involved in inhibiting heparin-mediated angiogenesis in wounded tissue. Finally, mast cells may play a role in the extracellular matrix remodelling, on the basis of in-vitro experiments (but there are still no in-vivo data).
We have examined the effects of oxygen free radicals, generated by xenobiotics administration, ischaemia-reperfusion or sepsis, on the healing of skin or intestinal wounds in rats. We found that 5 days after operation there was a significant decrease in the wound breaking strength in rats treated with phenazine methosulfate, zymosan, ischaemia-reperfusion or retroperitoneal infection. These changes were specifically prevented by administration of superoxide-dismutase (SOD), aprotinin and (in some models) allopurinol. On the contrary, none of these measures was effective when a local trauma caused the decrease in breaking strength. Our results suggest that oxygen free radicals mediate the inhibition of wound healing following ischaemia-reperfusion and sepsis.
There is a high incidence of wound dehiscence, ranging from 6.9% to 22%, after surgery for severe obesity. Different surgical techniques to minimize this drawback of the operation have been proposed, but none have seemed to be really effective. A different approach to this problem has been tried using topical treatment with hyaluronic acid through the drains of the laparotomy suture. Twenty patients subjected to jejuno-ileal by-pass for severe obesity were randomized into two treatment groups: hyaluronic acid (80 mg/daily) or placebo (saline), for 5 days, starting at the operation. Granulation tissue was withdrawn from the wound through polyvinyl catheters 1, 3 and 5 days after the operation. It was processed for light, scanning and transmission electron microscopy. Ten days after the operation, the wounds were examined for dehiscence. Hyaluronic acid treatment reduced the incidence and degree of dehiscence macroscopically, increased the maturation of granulation tissue during the first post-operation days and stimulated fibroblasts to synthesize procollagen shortly after the operation.
We studied the effect of a new prostaglandin analogue, 9-hydroxy-19,20-bis-norprostanoic acid (rosaprostol), on the duodenal mucosa of humans after administration of 40% ethanol. Eighteen healthy volunteers entered the study, which followed a blind cross-over design. At time 0 all the volunteers received rosaprostol or placebo; 5 minutes later, 40% ethanol (50 ml dose) was given. The mucosa was examined for lesions 3, 60 and 180 min later under endoscopy, light and scanning microscopy. It was found that: (i) 40% ethanol damaged the duodenum, with blood extravasation, inflammation and necrosis of the mucosa, (ii) rosaprostol significantly protected the mucosa 3 min after 40% ethanol, and (iii) the damage became worse after 3 h when placebo was given, whereas it was reduced after 1 h when PG was administered. The results suggest that PGs not only protect the mucosa against ethanol damage, but also stimulate its recovery.
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Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication.