Charcoal deposits in the esophageal and gastric mucosa

We report the case of a 75-yr-old woman referred for gastrointestinal endoscopy to investigate severe iron deficiency anemia. Black linear lesions were observed in the distal esophagus and stomach. Biopsies revealed aggregates of coarse black foreign material, which was later identified as charcoal. The patient's previous medical history included an antidepressant overdose 5 yr before the current admission. The patient had a gastric lavage, using a large bore orogastric tube, followed by the administration of activated charcoal. The patient had no other history of charcoal ingestion. We propose that the charcoal became entrapped in mucosal tears caused by the traumatic intubation 5 yr previously, causing the incidental mucosal tattooing seen at endoscopy.     

Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.     

Evaluation of treatment for the prevention of acute gastric lesions in stress, in rats

Since portal hypertension affects the gastric mucosa, leading to congestive gastropathy and thus to increased incidence of bleeding, it is one of the possible causes of increased permeability of gastric mucosal capillaries. The aim of this study was the quantitative assessment of the permeability of the gastric mucosal endothelial cells. Eight CCl4-induced cirrhotic rats and eight matched controls were subjected to i.v. injection of FITC-albumin, and a morphometric evaluation of fluorescence in serial histological sections of the gastric mucosa was performed by a video image analysis system. Fluorescence was found to be 0.351 +/- 0.01% of the area scanned in experimental animals versus 0.073 +/- 0.005% in controls, i.e. it was significantly increased by the treatment, which implies a significant endothelial leakage into the extravascular space.     

Urethroplasty of the free colonic mucosa in rats. Preliminary study of the use of appendicular mucosa

The various tissues used as free grafts in urethroplasties are associated with a high incidence of fistulae and strictures. The search for a new, more effective substitute had led the authors to study the possibility of using a new type of mucosa: appendicular mucosa. The size and cylindrical structure of the appendix and its easy resection make it an original and adapted urethral substitute. As most animals do not possess an appendix, an animal model of urethroplasty with colic mucosa has been used. A segmental distal urethrectomy has been performed on 40 rats, 14 had a simple urethral stent without any urethroplasty (Group I), for 7 wi performed the urethroplasty with a collagen tube (Group II) and for 19 an urethroplasty with free colic mucosa was performed (Group III), 3 to 6 weeks later, a macroscopic and microscopic study were realised. In group I and II the urethral duct developed a fibrosis and all rats had a severe stenosis when the stent went out. In those two groups, a urinary fistula has been developed in all rats except one. In group III, a neo-urethra was found. Under light microscopic examination a typical urothelium was observed in the mid and distal section and a keratinized squamous epithelium on the distal section. The results of the preliminary study let us believe that the digestive mucosa may be used for urethroplasty. Before we can propose the appendix mucosa in human surgery, it will be useful to perform sooner histological examination, then the genesis of the neo-urothelium should be understood.     

Concurrent radiotherapy and chemotherapy with protracted continuous infusion of 5-fluorouracil in inoperable esophageal squamous cell carcinoma

PURPOSE: The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. METHODS AND MATERIALS: Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. RESULTS: For 25 patients receiving a total dose of > or = 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. CONCLUSION: The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma.     

Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium

BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally.     

Epidermization in the esophageal mucosa: unusual epithelial changes clearly detected by Lugol's staining

A 58-year-old Japanese man with superficial esophageal cancer accompanied by unusual epithelial changes, including esophageal mucosal epidermization, is reported. Staining with Lugol's iodine clearly showed irregular unstained lesions, which could not be seen clearly macroscopically, in the resected specimen. Histologic examination of the irregular unstained areas showed definite granular and horny layers regarded as epidermization, acanthosis with slight nuclear enlargement, and epithelial atrophy. The immunohistochemical staining patterns of keratins in the epidermized and atrophic lesions were similar to those in the epidermis, and the keratin staining patterns of the acanthotic lesion were similar to those of the oral epithelium.     

Evaluation of T-lymphocytes in esophageal mucosal biopsies

OBJECTIVE: To modify and improve a protocol for surveillance of patients presenting for routine elective abortion services. METHODS: Six hundred seventy-four women presenting for routine elective first-trimester abortions were studied. All were 84 or fewer days after the last menstrual period, had no history of bleeding, and had positive urine pregnancy tests. Each woman was scanned initially with an empty-bladder transabdominal technique. If no sac was seen, endovaginal ultrasonography was performed. All terminations had modified gross examination of tissue (3x magnification) as well as staining for microscopic analysis. RESULTS: Six hundred twelve patients (90.8%) demonstrated intrauterine gestations on transabdominal ultrasound, 595 of which were 12 or fewer weeks. Suction and sharp curettage and examination of tissue revealed products of conception in all. Seventeen subjects (2.5%) were found to be 13 or more weeks despite bimanual examinations and last menstrual period suggesting 12 or fewer weeks. Sixty-two patients had no sac seen on transabdominal ultrasound, 34 of whom had definitive intrauterine gestations on endovaginal ultrasound. Curettage revealed chorionic villi in all. Two had unruptured definitive ectopic pregnancies seen on endovaginal ultrasound. Twenty-one women with no sac seen on endovaginal ultrasound underwent curettage as the next step in triage; chorionic villi proved an intrauterine gestation in 17. The additional four had decidua only on pathology. Rising hCG levels in two of these four led to a diagnosis of ectopic pregnancy, whereas falling hCG levels in the other two led to a presumptive diagnosis of complete abortion, possibly tubal pregnancy in light of the lack of vaginal bleeding. CONCLUSION: Pre-abortion sonography eliminates inadvertent second-trimester cases, and immediate postoperative examination of curettage material expedites the diagnosis of ectopic pregnancy when present.     

Cervical esophageal web associated with a patch of heterotopic gastric mucosa

Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed.     

Evaluation of changes in the course of seasonal allergic nasal mucosa inflammation

The efficacy, safety and diagnostic usefulness of adenosine in the treatment of supraventricular tachycardia in children were prospectively studied over a 2-year period. Only patients who were stable and without hypotension were included. Adenosine was given at a dose of 0.1 mg/kg and increased to 0.2 mg/kg for the second and third doses if there was no response. Adenosine was used on 5 occasions in 5 patients. Adenosine was found to be effective in terminating supraventricular tachycardia in all 5 patients; 4 responded to a dose of 0.2 mg/kg while 1 responded to 0.1 mg/kg. Wolff-Parkinson White Syndrome was detected in 2 patients after termination of supraventricular tachycardia. Transient hypotension was noted in 1 patient lasting 45 seconds with no haemodynamic consequences. Two patients had transient ventricular ectopics lasting 3 to 5 seconds. One out of 3 patients who were old enough to report side-effects, experienced chest discomfort and dizziness lasting 5 seconds. All side-effects were transient and mild. We concluded that adenosine is effective and safe in terminating supraventricular tachycardia in children after vagal manoeuvres have failed.     

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.     

Acute erosions of the gastric mucosa in burned rats: effect of sucralfate

Endometriosis remains a significant cause of pain and ill health for women and is a significant factor in reducing quality of life for women. The ability of desquamated endometrium to attach and implant within the peritoneal cavity is dependent upon its ability to establish and maintain an adequate blood supply. New vascularization is therefore a key part in the progression of endometriosis. Increased angiogenic activity is present in the peritoneal cavity of patients who suffer from the disease and more recently the potent angiogenic growth factor VEGF has been shown to be increased in the peritoneal fluid in patients with this disease. Whilst the desquamated endometrium itself under the influence of hypoxia further to retrograde menstruation is a likely rich source of VEGF, activated peritoneal fluid macrophages and infiltrating macrophages are also a rich source of this angiogenic growth factor. Surprisingly, steroidal regulation of macrophage expression of VEGF also appears to be a feature of this disease.     

Characterization of antichemotactic factor extracted from the gastric mucosa of rats

The gastric mucosa of normal rats exhibits no detectable inflammation or visible damage. We examined the effect of the gastric mucosal extract of rats on neutrophil chemotaxis and tried to purify antichemotactic factor. The chemotaxis of neutrophils was examined by the modified Boyden's method. After mucosal layer was scraped and then homogenized and centrifuged at 20,000 x g for 30 min, the supernatant was used as rat gastric mucosal extract (RGME). Prior exposure of neutrophils to the gastric mucosal extract caused a dose-dependent reduction in the neutrophil migration induced by formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) and interleukin 8 (IL-8) without affecting the cell viability. The antichemotactic factor was partially purified by lectin affinity chromatography on wheat germ lectin (WGL)-Sepharose, anion exchange chromatography on Mono-Q and gel filtration on Superose 12. The molecular weight of the antichemotactic factor was estimated to be around 60 k by gel filtration. The activity was markedly abolished by boiling for 5 min, heating at 60 degrees C for 30 min, and treatment with 1% acetic acid, 0.1 M Na2CO3 or trypsin. Furthermore, the FMLP-induced migration of neutrophils pretreated with the antichemotactic factor for 5 min followed by washing with fresh medium was inhibited, although the factor was not added to the chamber. These results suggest that the gastric mucosa of rats intrinsically generates an antichemotactic factor which might play a crucial role in maintenance of the integrity of the gastric mucosa.     

Synergistic effect of hydrochloric acid and bile acids on the pars esophageal mucosa of the porcine stomach

OBJECTIVES: To determine effects of finely ground diet and food deprivation on pH and bile acid concentration in the proximal portion of the porcine stomach and effects of bile acids and pH on the pars esophageal mucosa in vitro. ANIMALS: Sixteen 15- to 30-kg pigs. PROCEDURES: Gastric content samples obtained from pigs fed a finely ground pelleted or coarsely ground meal diet were assayed for gastric pH and bile acids. Stratified squamous epithelium was studied in an Ussing chamber, and histologically. Electrical conductance and transmucosal mannitol fluxes (as indices of tissue permeability) were determined at pH 4.0, 2.0, and 1.5 and in response to treatment with 0, 1, 2, or 3 mM taurodeoxycholate or glycocholate. RESULTS: Pigs fed the finely ground feed had significantly (P = 0.01) lower proximal stomach pH than did pigs fed the coarse meal. Proximal stomach bile acids concentration was significantly (P = 0.04) higher in pigs fed the finely ground diet. The H+ and bile acids concentration increased with time after feeding. In vitro exposure of the stratified mucosa to high H+ (pH < 4.0) and bile salt concentration (> or = 1.0 mM) resulted in significant (P < 0.05) dose-dependent increase in tissue conductance and mannitol fluxes, whereas low pH or bile acids alone had little effect. CONCLUSIONS: High H+ and bile acids concentration in the stomach of pigs fed finely ground diets or subjected to feed deprivation may contribute to ulceration of the pars esophageal tissue. Bile acids act synergistically and in dose-dependent manner, with low pH causing damage to the stratified squamous epithelium in vitro.     

Adaptive changes in intestinal mucosa of the small intestine as a result of intraluminal stress

Under physiological conditions, the intestinal mucosa is the site of a delicate balance between cell proliferation in the crypt region and cell desquamation at the villus tips. This balance can be deranged by a number of endogenous or exogenous factors, oneof which is the intraluminal contents. This review discusses the effects of different modifications of the luminal milieu on the structure and function of the mucosa. Following intestinal resection or loop transposition, the contents reaching the remnant or the transposed loop differ markedly from those with which they come into contact under normal conditions. Hyperplasia without zonal transformation then develops in the experimental loop. The villi do not become wider, and changes in the strucutre of the epithelium are not observed. There are conflicting resutls in the literature concerning the enzyme activities in the individual enterocytes resulting from this hyperplasia. However, the epithelium its functionally immature, since transport capacities measured in vitro are reduced. On the other hand, the hyperplasia of the mucosa is such that absorptive capacities in vivo, when expressed in terms of intestinal length, are larger than normal. When the intestine is subjected to prolonged infusion of lactic acid, the enterocytes are damaged and increased exfoliation results. A similar result is obtained in the blind-loop syndrome, where the accumulation of bile acids and bacteria provides the stress responsible for the destruction of the enterocytes, and in non-tropical spure, where the epithelium is attacked by noxious peptides in the diet. The first consequence of the accelerated desquamation is epithelial hyperplasia without zonal transformation, though the enterocytes are damaged - in contrast to those of the resected intestine - and apparently possess reduced enzyme activities. If the application of the stress is continued, a stage is reached in which the cell proliferation does not suffice to counteract the cell loss at the villus tips. Then a zonal transformation occurs whereby, despite the lengthened crypts, the villi become shorter and wider until, in extreme cases, the mucosa is completely devoid of villi. The transport capacity in vitro and in vivo - even when expressed in terms of unit-length is reduced, and good correlations exist between the reduction in function and the diminution in surface area of the intestine. In a self-emptying blind loop, the intestine is devoid of all contact with nutritional material. Under these circumstances, hypoplasia of the mucosa develops in which the enterocytes appear unchanged, though in extreme cases they may possess reduced enzyme levels, and the absorption capacity in vivo is consequently reduced.     

Reversibility of the curdlan feeding effects on the morphological structure of intestinal mucosa in rats

We reported in the previous paper that rats fed a curdlan diet showed significant increases in the weight of the cecum and its contents, a decrease in fecal wet weight, a retardation in the transit time of the gastrointestinal tract and morphological changes of the ileal and cecal mucosal surface when compared with the rats fed a cellulose diet. In the present study, we intended to learn if the curdlan effects on the morphological structure of intestinal mucosa were reversible. When rats were fed on the curdlan diet for 2 weeks followed by a cellulose diet for another 2 weeks, the cecum and cecal contents were not different from those of the cellulose group. The transit time of the gastrointestinal tract of the curdlan-followed-by-cellulose group was shorter than that of the curdlan group, whereas it was longer than that of the cellulose group. In scanning electron micrographs, the ileal villi of the curdlan-followed-by-cellulose group were normal, as in the cellulose group. However, their ileal and cecal microvilli were similar to those of the curdlan group, that is, the microvilli were crowded and more tightly packed, and some appeared to have been squeezed out. From these results, it was concluded that the effects of the curdlan feeding were only partially reversible, but the effects on the surface structure of intestinal mucosa were still sustained even after curdlan feeding of 2 weeks was discontinued. This might result from response to the high viscosity of the intestinal contents remaining after discontinuation of the curdlan.     

Effects of curdlan and gellan gum on the surface structure of intestinal mucosa in rats

The effects of curdlan and gellan gum on the gastrointestinal function were studied, and the morphological structure of the intestinal mucosal surface was observed by scanning electron microscopy of rats fed curdlan and gellan gum diets for four weeks. The rats fed the curdlan diet showed a significant increase in the weight of the cecum and its contents and a decrease in fecal weight as compared to the rats fed a cellulose diet. On the other hand, the rats fed the gellan gum diet showed a weight loss in cecal contents and weight gain in colonic contents. The transit time of the gastrointestinal tract was extended by curdlan supplementation whereas it was shortened by gellan gum supplementation. The surface structures of the ileal and cecal mucosa were markedly abnormal in the rats fed the curdlan diet: the microvilli were tightly packed and had fallen out at places. In the gellan gum-fed rats, the tops of the ileal and cecal microvilli adhered to one another and were covered with their contents. There was no difference in the surface structure of colonic mucosa among the cellulose, curdlan and gellan gum diet groups.     

Alpha-difluoromethylornithine inhibits N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in zinc-deficient rats: effects on esophageal cell proliferation and apoptosis

Sustained, increased cell proliferation induced by dietary zinc deficiency in rats plays a critical role in esophageal carcinogenesis. It is the determining factor that converts an otherwise nontumorigenic dose of N-nitrosomethylbenzylamine (NMBA) into a highly tumorigenic one. We studied whether the increased esophageal cell proliferation and susceptibility to NMBA-induced carcinogenesis induced by zinc deficiency can be inhibited by alpha-difluoromethylornithine (DFMO), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (the first enzyme in polyamine synthesis). Weanling rats were divided into four groups: Zn+/DFMO-, Zn+/DFMO+, Zn-/DFMO-, and Zn-/DFMO+. They were fed ad libitum either a zinc-sufficient (Zn+, 75 ppm zinc) or a zinc-deficient (Zn-, 4 ppm zinc) diet and given either deionized water (DFMO-) or 1% DFMO in deionized water (DFMO+). After 5 weeks, 5-19 animals from each group were sacrificed after in vivo 5-bromo-2'-deoxyuridine labeling to detect cells in S phase. The remaining animals in each group were given a single intragastric dose of NMBA at 2 mg/kg and sacrificed 12 weeks later for tumor incidence analysis. At week 5, DFMO treatment greatly decreased (by 48-82%) the levels of putrescine and spermidine in rat esophagus, colon, and liver, irrespective of dietary zinc intake. The increased esophageal cell proliferation induced by dietary zinc deficiency, as measured by the labeling index, the number of labeled cells, and the total number of cells, was substantially reduced by DFMO. This was accompanied by an increase in the rate of apoptosis. In addition, the expression of bax protein, an apoptosis accelerator, was markedly stronger in esophagi from Zn-/DFMO+ animals that showed increased apoptosis, whereas increased expression of bcl-2, an inhibitor of apoptosis, was only seen in the highly proliferative, zinc-deficient esophagus (Zn-/DFMO-). At week 12 after NMBA dosing, DFMO reduced the incidence of esophageal tumors from 80 to 4% in zinc-deficient rats. Our data showed that DFMO effectively inhibited the increased esophageal cell proliferation induced by dietary zinc deficiency and reduced the incidence of esophageal tumors induced by a single dose of NMBA in zinc-deficient animals. Our results also indicate a role for increased apoptosis in the mechanism(s) whereby DFMO brings about the inhibition of cell proliferation and tumor induction. These findings support a role for DFMO as a chemopreventive agent.