Fluticasone propionate for treatment of esophageal lichen planus. A case series.

Esophageal lichen planus is a rare condition, and although the majority of cases occur in conjunction with lichen planus at other sites, the endoscopic features are often misinterpreted resulting in a delay in diagnosis. We report a series of five patients presenting to our unit between 2005 and 2009. All five patients were female and presented with dysphagia. Endoscopy demonstrated proximal esophageal stricturing in four patients. Characteristic histological findings were found in four patients. Lichen planus was diagnosed at other sites, and preceded gastrointestinal symptoms, in all patients; five had oral involvement, two had genital involvement, and one had dermal involvement. All patients received proton pump inhibitor therapy without demonstrable benefit. Administration of oral fluticasone proprionate resulted in symptomatic improvement in three patients.

Preoperative chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: influence of emergent versus elective procedures on patient survival and tumor recurrence rate.

Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACE tumor necrosis and survival and recurrence rates. Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT. The decreased survival in the immediate and no-TACE groups was due to non-cancer-related deaths.

Azathioprine for maintaining remission of Crohn's disease.

OBJECTIVES: To assess the effectiveness of azathioprine in maintaining remission of quiescent Crohn's disease. SEARCH STRATEGY: Pertinent studies were selected using the MEDLINE data base (1966 - May 1998), the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, as well as abstracts from major gastrointestinal research meetings and references from published articles and reviews. SELECTION CRITERIA: Five randomized, double-blind, placebo-controlled trials of azathioprine therapy were identified. Two of these trials consisted solely of patients with quiescent Crohn's disease. Three trials had multiple therapeutic arms for both induction of remission and maintenance of remission. DATA COLLECTION AND ANALYSIS: Data were extracted by three independent observers (GRM, GF, LRS) based on the intention to treat principle. Peto odds ratios for the overall maintenance of remission, steroid sparing, and withdrawals due to adverse effects were calculated, and from these, 95% confidence intervals were derived. Numbers needed to treat or harm (NNT, NNH respectively) for the maintenance of remission, steroid sparing, and withdrawals due to adverse effects were also determined. MAIN RESULTS: Azathioprine had a positive effect on maintaining remission. The Peto odds ratio for maintenance of remission was 2.16 (CI 1.35 - 3.47) with an NNT of 7. A higher dose improved response. A steroid sparing effect was noted, with a Peto odds ratio of 5.22 (CI 1.06 - 25.68) and NNT of 3 for quiescent disease. The Peto odds ratio for withdrawals due to adverse events was 4.36 (CI 1.63 - 11.67), the NNH (Number Needed to Harm) was 19. REVIEWER'S CONCLUSIONS: Azathioprine is effective in maintaining remission. There is evidence for a steroid sparing effect.

C1 inhibitor deficiency and angioedema of the small intestine masquerading as Crohn's disease.

A case of C1 inhibitor deficiency presenting as localized edema of the small intestine is described. A 16-year-old, previously healthy woman presented with recurrent attacks of abdominal pain and vomiting following minor abdominal trauma. Investigations including computed tomography scan and barium studies confirmed localized edema of the jejunum. At laparoscopy, Crohn's disease was suspected; however, a subsequent enteroscopy was normal. Complement levels revealed a low C4 level, and C1 inhibitor deficiency was later confirmed. Attacks of abdominal pain began after starting oral contraceptives and have not returned since stopping the birth control pill. This rare cause of abdominal pain is examined, and C1 inhibitor deficiency and angioedema are reviewed.

Gastrointestinal complications in bone marrow transplant patients.

Complications of bone marrow transplantation are numerous, multifactorial and may affect any organ in the body. The involvement of the gastrointestinal system represents one of dominant sites of complications. Clinical management of gastrointestinal complications can be challenging in these patients. This overview summarizes common bone marrow transplantation related conditions affecting esophagus, stomach, small and large intestine as well as liver. These are discussed primarily from the clinical point of view with emphasis on the differential diagnosis. The histomorphologic features of these conditions are discussed as well.

Inhibition by lifarizine of intracellular Ca2+ rises and glutamate exocytosis in depolarized rat cerebrocortical synaptosomes and cultured neurones.

1. The effects of lifarizine (RS-87476) on intracellular Ca2+ rises and the release of glutamate from rat cerebrocortical synaptosomes depolarized with 30 mM KCl were investigated by use of entrapped fura 2 and exogenous glutamate dehydrogenase. 2. Prior (1 min) addition of lifarizine decreased 30 mM KCl-induced total glutamate release, with 3 microM and 10 microM causing 39% and 72% averaged decreases from controls. The calcium-dependent component of glutamate release (approx. 40% of total) was similarly decreased by 47% and 74%, whereas the calcium-independent component was decreased by only 32% and 43% respectively. 3. In parallel experiments with fura-2-loaded synaptosomes, lifarizine reduced the depolarization-induced increases in intracellular [Ca2+], suggesting that this is the means by which the decreases in glutamate release are brought about. Lifarizine inhibited both the plateau and the spike phases of the Ca2+ increases suggesting that, in addition to its known sodium channel blocking properties, it may also inhibit more than one class of calcium channel in the synaptosomes. 4. Lifarizine at 1 microM and 3 microM also inhibited the rises in intracellular [Ca2+] in rat cultured cortical neurons depolarized with 60 mM KCl. 5. These effects of lifarizine on intracellular Ca2+ and glutamate exocytosis may contribute to its neuroprotective action.

On the roles of long-chain acyl carnitine accumulation and impaired glucose utilization in ischaemic contracture development and tissue damage in the guinea-pig heart.

It has been proposed that the presence of increasing concentrations of fatty acids may accelerate the development of ischaemic contracture and cardiac damage, and that this may be due to long-chain acyl carnitine accumulation and/or impairment of glucose utilization. In isolated guinea-pig papillary muscles, palmitoyl (DL) carnitine was found to have a positive inotropic effect, with a slow onset of action suggestive of an intracellular site of action, and with a maximal effect of about two-fold at a concentration of 5-10 microM; higher concentrations led to decreased contraction, probably due to increasing detergent-like effects. In isolated fura-2-loaded chick cardiomyocytes, palmitoyl carnitine increased intracellular [Ca2+]; it is proposed that this is the means by which it increases contraction. The main hypothesis above was studied using isolated guinea-pig hearts perfused with either 11.7 mM or 5 mM glucose, and either albumin alone (3%) or albumin bound palmitate (1.5 mM) during low-flow ischaemia (92% reduction in flow) for up to 60 min. With 11.7 mM glucose, the presence of palmitate caused contracture development and increased enzyme release during ischaemia. Contracture also developed when the glucose concentration was reduced to 5 mM in the absence of fatty acid, however, in its presence contracture developed to a greater extent and with increased enzyme release. Long-chain acyl carnitine accumulation was similar in both groups. These studies show that long-chain acyl carnitine accumulation has the potential to induce contracture during ischaemia, although a reduction in glucose availability may also contribute.

Meta-analysis of the role of oral contraceptive agents in inflammatory bowel disease.

Numerous epidemiological studies have been performed to determine factors that might contribute to the development of inflammatory bowel disease. Although the role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis (UC) have been assessed, most studies were of small sample size and characterised by low statistical precision. A meta-analysis was performed to increase the statistical power and to investigate the association between the use of oral contraceptives and the development of CD and UC. The study was based on a search of a Medline database from 1975 to October 1993 and a review of reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. All studies specifically designed to evaluate this association were selected. The combined results of nine studies--two cohort studies (30,379 unexposed and 30,673 exposed patients) and seven case-control studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection criteria were evaluated. The pooled relative risk (adjusted for smoking) associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29 (0.94, 1.77) for UC. These results suggest modest associations between the use of oral contraceptives and the development of CD and UC. As these associations are weak, non-causal explanations for the findings cannot be eliminated.

PIP: The GI Research Group of the University of Calgary in Alberta, Canada, used data from seven case control studies (719 cases of inflammatory bowel disease and 3198 controls) and two cohort studies (32,673 users of oral contraceptives [OCs] and 30,379 nonusers) to conduct a meta-analysis to increase the statistical power to examine the association between OC use and the development of Crohn's disease (CD) and ulcerative colitis (UC). The studies tended to have a small sample size and a low statistical power. The estimated relative risks (RRs) in the studies of CD varied from 0.7 to 2.5. The pooled RR for both cohort and case control studies of CD stood at 1.44 when controlled for smoking and 1.68 when not controlled for smoking. The confidence intervals in seven of the eight studies of CD and for all four studies of UC included unity. The RRs in the studies of UC ranged from 0.7 to 2.4. The pooled RR for the studies of UC were 1.29 when adjusted for smoking and 1.68 when not adjusted for smoking. The researchers controlled for smoking because smoking protects against UC and is a risk factor for CD. These findings suggest a positive, albeit modest, association between OC use and both CD and UC, even when smoking is controlled. Since the associations are modest, the GI Research Group could not eliminate non-causal explanations for the findings.

Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis.

PURPOSE: To assess the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn disease and the effectiveness of azathioprine in maintaining remission of quiescent disease. DATA SOURCES: Pertinent studies were selected from the MEDLINE database (1966 to May 1994), abstracts from major gastrointestinal meetings, and references from published articles and reviews. STUDY SELECTION: Nine randomized, placebo-controlled trials of azathioprine or 6-mercaptopurine therapy were identified: Four addressed active disease, two addressed quiescent disease, and three had multiple therapeutic arms. DATA EXTRACTION: Data were extracted by three independent observers on the basis of the intention-to-treat principle and were analyzed with logistic regression. Each study was given a quality score on the basis of predetermined criteria. DATA SYNTHESIS: Compared with placebo, azathioprine or 6-mercaptopurine therapy had an odds ratio of response of 3.09 (95% CI, 2.45 to 3.91) in patients with active Crohn disease. When the single trial that used 6-mercaptopurine in active disease was excluded from the analysis, the odds ratio of response was 1.45 (CI, 1.12 to 1.87). No trials of quiescent disease used 6-mercaptopurine; the odds ratio of response in these trials of quiescent disease was 2.27 (CI, 1.76 to 2.93). For active disease, continuation of therapy for at least 17 weeks improved response (P = 0.03). For quiescent disease, a higher dose improved response (P = 0.008). Increased cumulative dose improved response in both groups (P < 0.001 for active disease and P = 0.01 for quiescent disease). A steroid-sparing effect was seen in active disease (odds ratio, 3.69 (CI, 2.12 to 6.42) and in quiescent disease (odds ratio, 4.64 [CI, 1.00 to 21.54]). Fistulae improved with therapy (odds ratio, 4.44 [CI, 1.50 to 13.20]). Adverse events requiring withdrawal from a trial, primarily allergy, leukopenia, pancreatitis, and nausea, were increased with therapy (odds ratio, 5.26 [CI, 2.20 to 12.60]). CONCLUSIONS: Azathioprine and 6-mercaptopurine are effective in treating active Crohn disease and in maintaining remission. Cumulative dose was an important factor in predicting response. Adverse effects were more common among patients receiving therapy.

Neuroprotective profile of lifarizine (RS-87476) in rat cerebrocortical neurones in culture.

1. The ability of the neuroprotective agent, lifarizine (RS-87476), to mitigate veratridine-, cyanide- and glutamate-induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)-MK-801 and (-)-MK-801. Lactate dehydrogenase (LDH) released into the culture medium was used as the indicator of cell viability. 2. Incubation of cultures for 16 h in a medium containing veratridine (10(-4) M), sodium glutamate (10(-3) M) or sodium cyanide (10(-3) M) resulted in consistent elevations of LDH activity in the culture medium. The ability of compounds to attenuate these elevations was expressed as the concentration required to inhibit the increases in LDH release by 50% (IC50). 3. Neurotoxicity induced by veratridine was inhibited by lifarizine (IC50 = 4 x 10(-7) M), TTX (IC50 = 3 x 10(-8) M) and nitrendipine (IC50 = 3 x 10(-5) M). In contrast, (+)-MK-801 (up to 3 x 10(-5) M) was ineffective against this insult. 4. Glutamate-induced neurotoxicity was inhibited by (+)-MK-801 (IC50 = 1.4 x 10(-8) M) and to a lesser extent by (-)-MK-801 (IC50 = 1 x 10(-7) M), but was unaffected by lifarizine, TTX or nitrendipine (up to 10(-6) M). 5. (+)-MK-801 was effective against sodium cyanide-induced neurotoxicity (IC50 = 1.9 x 10(-8) M), whereas lifarizine and TTX (up to 10(-6) M) and nitrendipine (up to 3 x 10(-6) M) were without protective activity against this insult. 6. The results demonstrate that lifarizine potently protects rat cortical neurones in vitro against a neurotoxic insult that requires activation of sodium channels for its expression, and that the compound is ineffective against insults mediated by N-methyl-D-aspartate receptor activation. The weak efficacy of nitrendipine against veratridine-induced cell death argues against the involvement of L-type calcium channels in this insult. These data are consistent with the notion that the neuroprotective activity oflifarizine observed in vivo may be mediated by inhibition of neuronal sodium currents.

The effect of propofol on the canine sphincter of Oddi.

To assess the effect of propofol on the canine sphincter of Oddi(SO), sphincter of Oddi manometry (SOM) was performed in fasting dogs which had undergone cholecystectomy and placement of modified Thomas duodenal cannulae. Using two water-perfused, single-lumen manometric catheters, SO and duodenal pressures were measured simultaneously. Baseline SO activity was recorded for at least one complete interdigestive cycle followed by bolus injections of propofol (Diprivan) (N = 31) from 0.1 to 4.0 mg/kg during Phase I of the Migrating Motor Complex (MMC). When propofol was administered in bolus doses < or = 0.4 mg/kg, no change in SO or duodenal motor function was seen. In doses > or = 0.5 mg/kg, SO basal pressure, amplitude, and frequency of contractions increased significantly. Increases in duodenal activity paralleled SO activity. Our results suggest that propofol in low doses may be useful for sedation during Sphincter of Oddi manometry in humans. Further studies of the effect of propofol on the human sphincter of Oddi are warranted.

Removal of stones from the bile duct at ERCP without sphincterotomy.

The main risks associated with endoscopic stone removal arise from the sphincterotomy that is performed to facilitate stone extraction. The complication rate may be higher when the bile duct is not dilated. Between January 30, 1990, and March 30, 1993, we attempted to remove stones up to 8 mm in diameter through the intact papilla, without performing sphincterotomy, in 24 patients. Nine patients underwent balloon dilation of the sphincter or of a low duct stricture to facilitate stone removal. All patients were treated successfully and are well at follow-up. Two patients (one having had balloon dilation of the sphincter) had mild pancreatitis that required 2 days in the hospital. During the same period, 215 patients were treated for duct stones 8 mm or less through a standard sphincterotomy. Complications occurred in 11 of these patients: five episodes of pancreatitis, three infections, one perforation, and two other complications. Although these two groups of patients are not directly comparable, it appears that selected stones can be extracted from the bile duct without sphincterotomy with relative safety. This technique should be studied further, especially in younger persons where sphincter preservation may be desirable.

Gastrointestinal symptoms in ambulatory HIV-infected patients.

Gastrointestinal symptoms are commonly seen in patients with established AIDS. We examined the charts of 258 HIV-infected patients attending our HIV outpatient clinic to determine: (1) the frequency of gastrointestinal symptoms in unselected HIV-infected patients and (2) if there are any predictors of the development of symptoms in initially asymptomatic patients. We found the overall frequency of gastrointestinal symptoms at initial presentation in our ambulatory, predominantly homosexual population of HIV-infected patients was 35% (95% CI 30-40%) with 19% having anorexia, 15% weight loss, 14% diarrhea, and 5% dysphagia. There was no association between the presence of symptoms and stool parasites, which were found in 51% of patients. In 165 patients who were initially asymptomatic, 72% subsequently developed symptoms over 36 months of actuarial follow-up. Patients with initial T4 counts < 500 were more likely to develop symptoms. Patients with a greater degree of immunosuppression as indicated by a lower T4 count, are more likely to develop gastrointestinal symptoms.

Is small intestinal permeability really increased in relatives of patients with Crohn's disease?

BACKGROUND: Patients with Crohn's disease have increased intestinal permeability, which may precede the development of clinical disease and be involved in disease pathogenesis. Subsequent studies have suggested that, as a group, first-degree relatives of patients with Crohn's disease do not have significantly increased small intestinal permeability rates. The present study proposes that conventional data analysis, used in these studies, may be inappropriate and has overlooked an important observation. METHODS: Lactulose and mannitol permeabilities were defined in healthy controls and in patients with Crohn's disease and their first-degree relatives. RESULTS: Intestinal permeability in relatives was similar to that in the control group, but a subpopulation had abnormally high permeability rates in the absence of clinical evidence for disease. Raw data from another investigator confirmed this finding in an additional study; consequently, it is concluded that the original hypothesis is still viable. A small proportion of individuals, at high risk of developing Crohn's disease, have increased intestinal permeability. CONCLUSIONS: Increased intestinal permeability may precede clinical manifestations of Crohn's disease.

Sulfasalazine revisited: a meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis.

PURPOSE: To assess the effectiveness of the newer 5-aminosalicylic acid (5-ASA) delivery systems compared with placebo or sulfasalazine for the treatment of active ulcerative colitis and for the maintenance of remission. DATA SOURCES: Pertinent studies were selected using the MEDLINE and BIOS (1981 to 1992) data bases, reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. STUDY SELECTION: Randomized controlled trials of 5-ASA compared with placebo or sulfasalazine of a minimum of 4 weeks duration for active disease and a minimum of 6 months for maintenance of disease remission. Sixteen trials of 5-ASA for active disease, published either in abstract or full manuscript, were available. Eleven trials of 5-ASA for maintenance of remission were also reviewed. DATA EXTRACTION: Crude rates for either induction of remission (active disease studies) or maintenance of remission (relapse-prevention trials) based on the intention-to-treat principle were extracted from the studies by two independent observers. Each study was given a quality score, based on predetermined criteria. RESULTS: Studies were placed in three groups: 5-ASA compared with placebo, 5-ASA compared with sulfasalazine for active disease, and 5-ASA compared with sulfasalazine for maintenance of remission. 5-Aminosalicylic acid was superior to placebo in the treatment of active ulcerative colitis (pooled odds ratio, 2.02; 95% CI, 1.50 to 2.72). A dose-response effect for 5-ASA existed (P < 0.001). For active disease, the pooled odds ratio for 5-ASA compared with sulfasalazine was 1.15 (CI, 0.83 to 1.61). When 5-ASA was compared with sulfasalazine for maintenance of disease remission, the pooled odds ratio was 0.85 (CI, 0.64 to 1.15). Withdrawal rates and reported side effects were similar for 5-ASA compared with placebo- or sulfasalazine-treated patients. CONCLUSIONS: Although the newer 5-ASA preparations in a dose of at least 2 g/d are more effective than placebo in the treatment of ulcerative colitis, insufficient evidence exists to suggest that they are superior to sulfasalazine. Although they offer a benefit to the sulfasalazine-sensitive patient, use of 5-ASA preparations instead of sulfasalazine in the treatment of ulcerative colitis cannot yet be substantiated.