Quantification of gastric ulcer healing by endoscopic ultrasonography

We studied and quantified the healing process of gastric ulcers in humans by means of endoscopic ultrasonography. Initially, using the water bath method, we scanned specimens of resected human stomachs with gastric ulcers including 9 open ulcers and 14 ulcer scars. Comparison of histological findings and measurement of the cross-section suggested that the ulcers observed in the ultrasonographic photographs were essentially equivalent to those in histological photographs. By using endoscopic ultrasonography, we then examined 16 patients with active, mainly recurrent, gastric ulcers before and after 2, 4, and 8 weeks of H2 blocker treatment, measuring the length and cross-sectional area of the ulcer in endoscopic ultrasonographic photographs. From measurements of the contraction rate of cross-sectional ulcer area during healing, we observed that the healed ulcers showed a relatively rapid rate of contraction in the first 4 weeks of therapy and the non-healed cases showed a poor contraction rate. Endoscopic ultrasonography is useful for the quantitative estimation of histological changes associated with gastric ulcer healing.     

Treatment of gastric ulcer with ranitidine

Forty-eight patients with endoscopically proven gastric ulcer were treated either with ranitidine tablets, 150 mg twice daily, or with placebo tablets under double-blind conditions. Three patients were for various reasons excluded from the study. After 6 weeks' treatment a second endoscopy was performed. The ulcer had healed in 22 (88%) of the 25 patients who had received ranitidine tablets and in 4 (20%) of the 20 patients who had received placebo tablets. The difference was statistically significant (p less than 0.002). The number of days and nights with pain attacks and the number of antacid tablets consumed were significantly (p less than 0.002) lower in the patient group treated with ranitidine. The 3 patients with non-healed ulcer after treatment with ranitidine had their ulcers healed after a further 6 weeks' treatment with ranitidine, and of the 16 patients with non-healed ulcer after treatment with placebo tablets, 13 had their ulcers healed after 6 weeks' open treatment with ranitidine, 150 mg twice daily. No serious side effects that could be ascribed to treatment occurred during the study.     

Effects of NC-1300, a gastric proton pump inhibitor,on healing of acetic acid-induced gastric ulcers in rats

Effects of NC-1300 (a gastric proton pump inhibitor) on healing of experimental chronic gastric ulcers induced in rats were studied. Gastric ulcers were induced by the submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of the anterior wall of male Donryu rats (260–280 g). The healing of acetic acid ulcers was delayed by the daily subcutaneous administration of indomethacin (1 mg/kg) for two or four weeks after ulceration. Aggravation of healed ulcers was evoked by subcutaneous administration of indomethacin (1 mg/kg) once daily for four weeks to rats with four-week-old ulcers. Oral administration of NC-1300 (10, 30, or 100 mg/kg) once daily for two or four weeks after ulceration dose-dependently accelerated both natural and delayed healing of acetic acid ulcers. When the period of administration was extended from two to four weeks, the ED₅₀ values (the dose reducing the ulcerated area by 50%) were decreased from 36.5 to 13.5 mg/ kg in natural healing and from 76.0 to 23.0 mg/kg in delayed healing. Aggravation of four-week-old ulcers by indomethacin was significantly prevented by daily administration of NC-1300 (30 or 100 mg/kg) for four weeks. Acetic acid ulcers that were healed with NC-1300 given for four weeks after ulceration remained healed for four to eight weeks after the cessation of drug administration. A single administration of NC-1300 to normal rats and repeated administration of NC-1300 to rats with acetic acid ulcers for four weeks after ulceration caused the same degree of inhibition of gastric acid secretion. Reduction in the area of ulceration and inhibition of gastric acid secretion by NC-1300 were significantly correlated in the indomethacin-treated animals. We conclude that NC-1300 markedly accelerates the healing of chronic gastric ulcers and prevents aggravation of the healed ulcers, presumably through antisecretory activities.     

Influence of Helicobacter pylori Infection on Healing and Relapse of Acetic Acid Ulcers in Mongolian Gerbils

Both Helicobacter pylori and NSAIDs play important roles in the healing and relapse of peptic ulcers in man. We examined how H. pylori infection, indomethacin, and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed gastric ulcers in Mongolian gerbils. Gastric ulcers were induced by serosal application of an acetic acid solution. H. pylori (ATCC43504) was orally administered once into animals with active and healed ulcers. Ulcers healed within eight weeks and remained healed for the following six months. H. pylori infection significantly delayed ulcer healing four weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected Mongolian gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from one to six months after infection, with a gradual increase in size. By the fourth month following a relapse, the serum gastrin level had significantly increased. H. pylori-induced ulcers in the posterior wall coexisted with relapsed ulcers in the anterior wall five and six months later. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. It is concluded that, in Mongolian gerbils, H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse.     

Gastric ulcer healing after laser treatment in dogs

Endoscopic laser photocoagulation of ulcers is increasingly used to produce hemostasis in patients who are actively bleeding or in patients with stigmata of recent hemorrhage. Little information is available describing ulcer healing rates after laser treatments. The aim of this study was to compare the healing rates of gastric ulcers treated with laser energy (Nd:YAG) with untreated ulcers in dogs. Two standard gastric ulcers (12-14 mm diameter) were created in each dog stomach using an ulcer maker (Quinton) under endoscopic guidance and one was randomly selected for laser treatment (L), while the other served as control (C). Ten laser spots were applied circumferentially around the ulcer crater with a mean energy of 595 J per ulcer. Ten dogs were studied; four of which were sacrificed after one week and six after two weeks. Healing of treated ulcers was compared with that of control ulcers and expressed as a percentage of the initial ulcer surface. Histologic injury and reepithelialization were scored by two pathologists unaware of the treatment. Laser-treated ulcers healed significantly slower than untreated ulcers at one week (53% L vs 94% C, P less than 0.05) and histologic injury was greater in ulcers treated with laser photocoagulation. At two weeks, only 82% of the laser-treated ulcer surface was healed in comparison with 94% (P less than 0.05) healing in untreated ulcers, although the mean histologic injury score was not different at two weeks. Reepithelialization was decreased both at one week (11% L vs 71% C, P less than 0.01) and at two weeks (75% L vs 100% C, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative Evaluation of Mucosal Regeneration in Gastric Ulcers by Electronic Endoscopy —Comparison between Tractable and Intractable Ulcers—

Abstract: The electronic endoscope named TGS-50B (TOSHIBA) provides a fine resolvable image (Fig. 6) and flat white balance covering a wide range (Fig. 7). Using this electronic endoscope, the regenerative mucosal patterns in 15 cases with intractable and 30 cases with tractable gastric ulcers (Table 1) were observed at 2-week intervals until the healed stage or until 12 weeks after the start of H₂-blocker administration. To clarify the difference between intractable and tractable gastric ulcers, the electronic endoscopic images were fed into an image analyzer; SPICCA (AVIONICS). The regenerative mucosal pattern was converted into 20 binary digited particles by the image analyzer (Fig. 4, Color) and quantified by the oval specification (OSF) value (Fig. 5). The OSF value of the tractable ulcers significantly increased in the healing stage I (H₁) and healing stage 2 (H₂), in comparison with those of intractable ulcers (Fig. 8). Moreover, the OSF value of the tractable ulcer significantly increased at 4 weeks after the start of an H₂-blocker, comparing with that at 2 weeks. Consequently, the OSF values of the tractable ulcers were significantly high in comparison with those of the intractable ulcers, at 4, 6 and 8 weeks after the start of administration of H₂-blockers (Fig. 9). By histological study of the biopsy specimen, an increase in the OSF value suggested an extension of the regenerative mucosa by a well progressed annular contraction of the gastric wall. In conclusion, it is thought that intractability of gastric ulcers may be objectively predictable in its early healing stages by determination of the OSF value using the electronic endoscope and the image analyzer.     

Histological maturity of healed duodenal ulcers and ulcer recurrence after treatment with colloidal bismuth subcitrate or cimetidine

The relationship between histological maturity of healed duodenal ulcers and ulcer recurrence after 6 weeks of treatment with colloidal bismuth subcitrate or cimetidine was investigated. There was no significant difference in healing rates between colloidal bismuth subcitrate- and cimetidine-treated patients (85.7% and 71.8%, respectively; P greater than 0.05). Histologically, the regenerating mucosa of healed ulcers was divided into three categories--good, fair, and poor--according to pattern. Sixty percent of healed colloidal bismuth subcitrate-treated and 30.9% of healed cimetidine-treated ulcers had a good pattern; the difference was statistically significant (P = 0.027). The difference in recurrence rates between healed colloidal bismuth subcitrate-treated and healed cimetidine-treated patients was statistically significant at 3 months (3.45% and 20%, respectively; P = 0.044). All recurrent ulcers in both groups had fair or poor patterns of regenerating mucosa. It was concluded that the greater histological maturity of the regenerating mucosa may contribute to the lower recurrence rate in colloidal bismuth subcitrate-treated patients than in cimetidine-treated patients.     

Effect of cimetidine treatment in the prevention of gastric ulcer relapse: a one year double blind multicentre study.

One hundred and forty six gastric ulcer patients were given open treatment using 1 g cimetidine daily to heal their ulcers. Of 130 who completed the acute treatment period of eight weeks, 112 (86%) had healed ulcers. Of these 112 patients with healed ulcers, 108 entered a one year double blind study to compare the effect of cimetidine maintenance therapy (400 mg at night) with placebo. Of the 84 patients available for assessment at the end of one year, 86% in the cimetidine treated group were in remission compared with 45% in the placebo treated group (chi 2 = 15.03; p less than 0.001). There were similar losses from non-compliance and drop out in both groups. The incidence of untoward effects and significant drug related laboratory abnormalities was low. The results indicate that cimetidine heals nearly 90% of acute gastric ulcers within eight weeks and that subsequent low dose maintenance treatment at night offers a considerable benefit over placebo therapy.     

Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime.

The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.     

Chronic mesenteric vascular insufficiency with gastric ulceration

Four middle-aged women presented with long histories of severe progressive weight loss and chronic abdominal pain. Endoscopically atypical gastric ulcers were identified in all; the ulcers were multiple and antral in location, with irregular shapes, sloping edges, and whitish sclerotic bases, and were surrounded by mottled and erythematous mucosa containing numerous superficial erosions. They did not heal with conservative therapy. All 4 patients were found to be suffering from chronic mesenteric vascular insufficiency. Balloon dilatation of the superior mesenteric artery in one and surgical revascularization in the others resulted in progressive clinical improvement and healing of the ulcers. The striking feature in these patients with mesenteric ischemia was the finding of gastric ulcers with a morphology different from the ordinary gastric ulcer, which healed only with revascularization. Future observation of similar lesions should suggest the possible diagnosis and expedite early treatment of mesenteric insufficiency in patients with this disorder.     

Double blind comparative study of omeprazole and ranitidine in patients with duodenal or gastric ulcer: a multicentre trial. Cooperative study group.

We studied omeprazole and ranitidine in promoting duodenal ulcer healing in a multicentre trial by comparing the proportion of healed ulcers after two, four, and eight weeks of treatment. Altogether, 194 patients (143 men) were randomly allocated according to a prearranged treatment schedule to either drug and were treated double blind. Each received 40 mg omeprazole in the morning and a ranitidine placebo morning and evening or 150 mg ranitidine morning and evening with an omeprazole placebo in the morning. A total of 188 patients (94 taking omeprazole, 94 taking ranitidine) completed the trial. Sixty four (68%) omeprazole treated and 45 (48%) ranitidine treated patients had healed ulcers at two weeks, 91 (99%) omeprazole treated and 79 (88%) ranitidine treated had healed ulcers by four weeks, and 91 (100%) omeprazole treated and 86 (97%) ranitidine treated patients had healed ulcers by eight weeks. The overall difference in healing rates was significant (p = 0.0008, Mantel-Haenszel test). The differences were significant also at two weeks (20%, 95% confidence interval 5.6 to 34.4, p less than 0.01) and at four weeks (11%, 95% CI 3.7 to 17.3, p less than 0.01), but not at eight weeks (3%, 95% CI -0.5 to + 7.3, p = 0.25), using the chi 2 statistic, the study having a power to detect a 20% difference on 90% of occasions. After two weeks of treatment complete symptom relief was observed in 70 (74%) patients receiving omeprazole and in 58 (62%) receiving ranitidine. Diary cards showed a significantly lower percentage of days with pain in the omeprazole treated group (7.4% v 21.4%, p < 0.02) when assessed over either the first two weeks or over weeks three and four treatment. A total of 144 patients with healed duodenal ulcer were followed up, with no treatment, for six months. At the end of this period 19 (26%) of 74 patients healed with omeprazole and 17 (24%) of 70 patients healed with ranitidine were still in remission. A similar protocol was used for 46 patients (25 men) with gastric ulcer who were randomly allocated to treatment with omeprazole or ranitidine as described above. Forty patients (16 omeprazole, 24 ranitidine) completed trial. Thirteen (81%) omeprazole treated and 14 (58%) ranitidine treated patients had healed ulcers at four weeks; at eight weeks 14 (93%) omeprazole treated and 20 (87%) ranitidine treated patients had healed ulcers. These differences were not significant at four weeks (p = 0.25) or eight weeks (p = 0.96). Twenty seven gastric ulcer patients were followed up for six months and seven (58%) of the 12 omeprazole healed and five (33%) of the 15 ranitidine healed patients were in remission at six months. Unwanted adverse events were trivial except for one fatality in a 67 year old women, who died from bronchopneumonia and myocardial ischaemia while receiving treatment with omeprazole, which was judged to be unrelated to her death.     

Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.     

Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy.

BACKGROUND: The relation between Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID)-associated peptic ulcers remains unclear; in particular, it is not known whether H pylori plays a part in the healing and recurrence of these ulcers. AIMS: To evaluate prospectively in a consecutive series of arthritis patients receiving longterm NSAID treatment the prevalence of peptic ulcer as well as the effect of H pylori eradication on the healing and recurrence of gastric and duodenal ulcer found. PATIENTS: Some 278 consecutive patients underwent gastroscopy with multiple biopsies of the gastric antrum and corpus for histological examination and rapid urease test. One hundred peptic ulcers (59 gastric ulcers, 39 duodenal ulcers, and two gastric ulcers concomitant with a duodenal ulcer) were found. Seventy per cent of these ulcers were H pylori positive. METHODS: According to their H pylori status, ulcer patients were randomised to one of the following treatments: H pylori negative ulcers received omeprazole 20 mg twice daily for four to eight weeks, whereas H pylori positive lesions were treated with omeprazole 20 mg twice daily plus amoxycillin 1 g twice daily (the second of these for the first two weeks) or omeprazole alone for four to eight weeks while continuing NSAID therapy. Patients with healed ulcers were endoscopically followed up for six months after stopping antiulcer therapy while continuing NSAIDs. RESULTS: Endoscopic healing rates for gastric and duodenal ulcers in the three different groups were similar both at four and eight weeks. H pylori eradication did not influence healing, which occurred in 14 of 20 (70%) of patients in whom H pylori was eradicated, compared with 14 of 17 (82%) of patients with persistent infection. Cumulative recurrence rates at six months did not statistically differ among the three different groups (27% in H pylori negative, 46% in H pylori positive, and 31% in those where H pylori was eradicated during the healing phase), although a numerical trend in favour of a higher recurrence rate in infected patients was evident. CONCLUSIONS: H pylori eradication does not confer any significant advantage on the healing of gastric and duodenal ulcers associated with longterm NSAID use. It remains to be established with certainty whether eradication may be helpful in the reduction of recurrence in a specific subset of NSAID associated ulcer.     

Observations on the histology of the gastric mucosa in chronic gastric ulcer

Histologic changes were studied in the gastric mucosa of 18 patients with a chronic, lesser curve, gastric ulcer. Biopsies were taken approximately 2 cm from the ulcer margin, and from the opposite wall of the stomach body. Morphologic appearances noted in the active phase of ulceration were found to persist during the healing process (12 patients) and, on follow-up study, at 6 to 10 weeks (5 patients). The ulcer failed to heal in 6 patients, 5 were treated surgically and another refused operation; all had persisting gastritis. Twelve patients had been treated with carbenoxolone, which did not appear to influence histology. The ability of the ulcer to heal in the presence of continuing gastritis, the persistence of gastritis after the ulcer healed and the lack of difference in the surrounding mucosa between healed and unhealed ulcers indicate that the relationship between the two lesions is uncertain.     

A case of candidal infection of gastric ulcers with characteristic endoscopic findings

While Candida infection is a common opportunistic infection, Candida-associated gastric lesions are far less frequent. We report a case of gastric ulcers due to candidal infection. A 73-year-old woman had ulcers refractory to treatment with a proton pump inhibitor (PPI) and Helicobacter pylori eradication. Endoscopic findings showed that this case involved 2 gastric ulcers with thick exudate mainly located in the fornix. Biopsy specimens from gastric ulcers revealed numerous Candida forms. The patient was treated with antifungal drugs and the ulcers healed completely on endoscopy. We should draw attention to our observation in elderly patients with gastric ulcers, and if we find gastric ulcers with such characteristic endoscopic findings, candidal infection of gastric ulcers should be considered.     

Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers.

In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.     

Therapeutic Success with the Suppression of Helicobacter pylori of Intractable Gastric Ulcers

Abstract: Three patients with a long history of gastric ulcers refractory to treatment first with an H₂-receptor antagonist, then with a prostaglandin E_t analogue plus an antagonist, and next with a proton-pump inhibitor, lansoprazole, were given amoxicillin together with an H₂-receptor antagonist, and the ulcers finally healed. The patients were men aged about 60, and two were smokers. Reduction of gastric acidity by lansoprazole may have been satisfactory in these patients because one dose of the drug raised the gastric pH to more than 3.0 for about 97% of the next 24h in all three of the patients, as by the continuous measurement of intraluminal pH. The gastric mucosa of these patients was found to be infected with Helicobacter pylori when tested at the end of treatment with this inhibitor. Their medication was changed from the proton-pump inhibitor to amoxicillin plus an H₂-receptor antagonist, and all of the ulcers healed within 6 weeks. H. pylori was not detected at the end of this treatment. These results indicate that reduction of gastric acidity alone was insufficient to cure the ulcers in these patients. H. pylori may be related to some ulcers being refractory to many antiulcer agents, even proton-pump inhibitors.     

Collagen biomechanics in cerebral arteries and bifurcations assessed by polarizing microscopy

Collagen is the main matrix protein of the artery wall. We have used the known correlation between collagen birefringence and its mechanical properties to assess the wall structural integrity in brain arteries and their bifurcation regions, which are the sites of formation of saccular aneurysms. Segments of 28 brain arteries, including bifurcations, were pressure fixed and sectioned in one of three orthogonal planes. Measurements were taken by polarizing microscopy of the birefringence of collagen fibers at the apex of bifurcations and in the main layers of the artery wall - adventitia, media and intima. Dimensional data were obtained of the layers in order to estimate wall properties. Along the apex of the flow divider we measured a narrow band of collagen (birefringence 30% higher than the adjacent adventitia) providing strength and stiffness in that region. There is a thin cell-free outer layer of the tunica media (mean thickness 11 microm) comprised of densely packed coaligned collagen with high birefringence. From the fiber birefringence and directional alignment of the individual layers we calculated that the adventitia contributes about one third of circumferential and almost all of longitudinal strength of intracranial arteries.     

Effects of Cimetidine on the Healing of Benign Gastric Ulcers

Summary: A prospective double-blind trial was undertaken to determine whether treatment with cimetidine influenced the healing of gastric ulcers in New Zealand patients. Ulcer size and healing was assessed by endoscopic examination.
Of the 30 patients who completed the trial, 15 were given cimetidine and 15 placebo. At six weeks, 60% of the patients on cimetidine had healed their ulcers, whereas only 20% of those on the placebo had healed ulcers (P < 0·05). Fewer patients taking cimetidine required antacids for symptom control than those on placebo treatment (P < 0·05).
The study confirmed that cimetidine treatment accelerates the healing of gastric ulcers.     

Healing pressure ulcers with collagen or hydrocolloid: a randomized,controlled trial

OBJECTIVES: To compare the effects of topical collagen and hydrocolloid on pressure ulcer healing. DESIGN: Randomized (allocation concealed), single-blind (outcome assessors), controlled trial with 8-week follow-up. SETTING: Eleven nursing homes in central Illinois. PARTICIPANTS: Sixty-five patient-residents with Stage II or III pressure ulcers: median age 83.1, median Braden score 12, 63% female, 80% Stage II ulcers, and 20% Stage III ulcers. Exclusion criteria included cellulitis and osteomyelitis. INTERVENTION: Thirty-five patients were allocated to topical collagen daily, 30 to topical hydrocolloid twice weekly. MEASUREMENTS: The primary outcome was complete healing within 8 weeks. Secondary outcomes were time to heal, ulcer area healed per day, linear healing of wound edge, and cost of therapy. RESULTS: Analysis by intention to treat revealed similar complete ulcer healing within 8 weeks in collagen (51%) and hydrocolloid (50%) recipients (difference 1%, 95% confidence interval (CI) = 26-29%). Mean healing time was similar: collagen healed in 5 weeks (95% CI = 4-6), hydrocolloid healed in 6 weeks (95% CI = 5-7). Mean area healed per day was 6 mm(2)/d in both treatment groups. Mean linear healing of the wound edge was 3 mm in both groups. In multivariate analysis, baseline ulcer depth was the only independent predictor of complete ulcer healing within 8 weeks (odds ratio = 0.56, 95% CI = 0.38-0.81). Cost analysis favored hydrocolloid. CONCLUSIONS: There were no significant differences in healing outcome between collagen and hydrocolloid. Collagen was more expensive and offered no major benefits to patients otherwise eligible for hydrocolloid treatment.