One-year adjustable intragastric balloons: results in 73 consecutive patients in the U.K.

BACKGROUND: Most intragastric balloons have 6-month approval. We report results with the Spatz Adjustable Balloon: approved for 12 months and adjustable. METHODS: Seventy-three patients (mean: age 45.5; weight 114.5 kg; BMI 36.6 kg/m2) scheduled for 1-year implantation with Spatz balloon (mean volume 417 ml saline). Adjustments performed for early intolerance and weight loss plateau. RESULTS: Three patients failed insertion. There were 21 early removals (4 intolerant refusing adjustment; 3 deflations; 14 satisfied patients) leaving 49 patients at 12 months. Results of 70 patients (49 patients at 12 months and 21 patients at <12 months) were a mean 21.6 kg weight loss; 19% weight loss; and 45.7% EWL (excess weight loss). Ten intolerant patients were adjusted and lost additional mean 13.2 kg. Fifty-one patients with weight loss plateau scheduled for adjustment: adjustments failed in 6 and non-response in 7. The adjusted 38 patients lost an additional mean 9.4 kg and at extraction had mean 40.9% EWL with 18.7% weight loss. Three catheter impactions required surgical extraction, and three deflated balloons didn't migrate beyond stomach. CONCLUSIONS: The Spatz balloon is an effective procedure without mortality; however, it carries a risk of catheter impaction necessitating surgical extraction (4.1%). The failure rate--4.1%; intolerance without ability to adjust balloon--5.5%; major complications occurred in 3 (4.1%); minor (balloon deflations) in 3 (4.1%), and 2 asymptomatic gastric ulcers at extraction (2.7%). The longer implantation period and adjustment option combine to produce greater weight loss, albeit <10% weight loss beyond the pre-adjustment weight loss.

A randomized placebo-controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease.

BACKGROUND & AIMS: alpha4 integrins are important mediators of leukocyte migration across vascular endothelium. This pilot placebo-controlled study aimed to assess the safety and efficacy of natalizumab, a recombinant humanized monoclonal antibody to alpha4 integrin, in patients with mild to moderately active Crohn's disease. METHODS: Thirty patients with active Crohn's disease (Crohn's Disease Activity Index [CDAI] > or =151 and < or =450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization. The study's primary endpoint was change in CDAI at week 2. RESULTS: At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points). Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo. In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients. Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration. The frequency of commonly reported adverse events did not differ significantly between groups. CONCLUSIONS: A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal. Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking. Natalizumab therapy in active Crohn's disease merits further investigation.

Auditing mortality from upper gastrointestinal haemorrhage: impact of a high dependency unit.

BACKGROUND: A retrospective audit conducted at our district general hospital indicated that mortality from upper gastrointestinal (GI) haemorrhage was above that reported from nearby centres. OBJECTIVES: To assess the impact of establishing a high dependency unit (HDU) and agreed management protocol on subsequent mortality from upper GI haemorrhage at our hospital. DESIGN: Prospective audits were conducted before and after the establishment of an HDU. All acute admissions, as well as established inpatients with haematemesis and/or melaena, were examined for fitness for endoscopy, comorbidity, underlying diagnosis and the need for surgery. SUBJECT: Over a two-year period, 524 patients were studied in the two audits. Risk scores were calculated and the 30-day mortality from all causes assessed. RESULTS: There was a trend towards higher age and comorbidity during the second audit. Mortality was 9% and 10% during the first and second audits, respectively. CONCLUSIONS: An increasing proportion of patients with bleeding are elderly and have associated comorbidity. Establishment of an HDU and agreed protocol did not reduce mortality at our centre.

Cross cover for physicians: an additional burden.

OBJECTIVE: To examine the extra burden placed on consultant physicians when providing cross cover for colleagues who are absent on annual or study leave. METHODS: A questionnaire was sent to 455 consultant physicians with an interest in gastroenterology, practising in the UK in October 1996. RESULTS: The response rate was 77%, with 350 completed forms returned. Ninety percent of respondents participate in the acute intake; they provide 85% of cross cover for their colleagues. Only 2% of this burden is carried by the appointment of locums. CONCLUSION: Provision of satisfactory cover for inpatients under the care of absent colleagues can place serious demands on consultants at a time when their specialty commitments are also high. Future manpower planning must take these added burdens into consideration.

Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.

One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.

Effect of nicotine on rectal mucus and mucosal eicosanoids.

Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel.

Cigarette smoking is not a risk factor in atopic dermatitis.

BACKGROUND: In recent years several diseases have been shown to have a relationship with smoking. Psoriasis is largely a disease of smokers, whereas acne appears to be associated with not smoking. METHODS: One hundred and fifty patients with atopic dermatitis were sent a postal questionnaire on smoking habits and the results were compared with those from matched controls in the local community. RESULTS: One hundred and twenty-seven patients (85%) completed the questionnaire. There was no apparent difference in the prevalence of current smokers amongst atopic dermatitis patients compared with controls (odds ratio = 1.1, 95% confidence limits 0.65-1.86, P = 0.8). CONCLUSIONS: There was no significant difference between the smoking prevalence of patients with atopic dermatitis and matched controls.

Smoking habits in psoriasis: a case control study.

We have examined smoking habits in 108 patients with psoriasis, including some with palmoplantar distribution, and compared the results with matched controls from the community. There was a significant association between psoriasis, current smoking status (OR = 2.7, 95% CI 1.44-5.42, P less than 0.01) and smoking habits prior to the onset of disease (OR = 3.75, 95% CI 1.68-9.47, P less than 0.001). There was also a marked dose-response relationship; the relative risk of psoriasis in those currently smoking more than 20 cigarettes/day was significantly elevated (OR = 5.3, 95% CI 2.1-13.0, P less than 0.001). Separate analysis of patients without palmoplantar distribution of psoriasis showed a significant association with smoking prior to onset of psoriasis (OR = 3.6, 95% CI 1.5-9.8, P less than 0.001). Smoking may play a role in the aetiology of this common skin disorder.

Incidence of ulcerative colitis in Cardiff over 20 years: 1968-87.

The annual incidence of ulcerative colitis in the city of Cardiff was examined over a 20 year period. In the decade 1968-77, the mean annual incidence was 6.4 per 10(5) of the population compared with 6.3 for the period 1978-87. There was no difference in the distribution or extent of the disease between decades or between sexes. This contrasts with the increased incidence of Crohn's disease during the same period. The study included a survey of family practitioners which identified a further 19 patients (11% of the total).

Smoking, humoral immunity, and ulcerative colitis.

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.

Prognostic implications of the localization of carcinoma in the head of the pancreas.

Between 1974 and 1989, 411 patients with pathologically and anatomically proven carcinoma of the head of the pancreas underwent endoscopic retrograde cholangiopancreatography (ERCP). According to the localization of the tumor, these patients were divided into those with a cranially, centrally (periductally), caudally, or indeterminately localized tumor. In cranially localized tumors, extrahepatic metastases and vessel invasion were absent or resectable in 53% and 46%, respectively. The tumor was resectable in 41% of cases. If a patient with a cranially localized tumor could not be operated curatively for secondary reasons, the prognosis was better than for tumors with another localization. If there was unresectable vessel invasion and the tumor was not resectable, the 0% survival rate was reached at 33 months. Of the curatively operated patients, 26% were alive at 36 months after the start of complaints. Of the centrally or periductally localized tumors, there were no liver metastases in 73%. Extrahepatic metastases and vessel invasion were absent or resectable in 57% and 53%, respectively. The tumor was resectable in 48% of cases. If there was unresectable vessel invasion or the tumor was unresectable, the 0% survival rate was reached after 18 months. These tumors have maximal chances at curative resection. Of the curatively operated patients, 31% were alive at 36 months after the start of complaints. In caudally localized tumors, there were liver metastases in 59%, unresectable other abdominal metastases in 93%, unresectable vessel invasion in 91%, and the tumor was unresectable in 96%. In patients with an unresectable vessel invasion or an unresectable tumor, the 0% survival rate was reached after 33 months; 3% of these patients were operated curatively. Indeterminately localized tumors had liver metastases in 77%, unresectable extrahepatic metastases in 90%, unresectable vessel invasion in 95%, and the tumor was unresectable in 91%. Only one of the 44 patients (2%) could be operated curatively.

Sensitivity and tolerance to nicotine in smokers and nonsmokers.

We studied the responses of smokers and lifelong non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n = 8), non-smokers on a 30 mg patch (n = 8) and smokers on a 30 mg patch (n = 8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD = 3.7), 10.9 (SD = 4.2) and 4.1 (SD = 2.7) ng/ml in the three groups, respectively (P less than 0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (X Cmax 13.9 ng/ml, SD = 4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P less than 0.01) within the first hour, and seven dropped out (P less than 0.01) at 3-8 h due mainly to severe nausea, vomiting or headache (X Cmax 18.4 ng/ml, SD = 4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (X Cmax 7.9 ng/ml, SD = 3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.

Stress management for irritable bowel syndrome: a controlled trial.

Thirty-five patients with irritable bowel syndrome were randomized to receive treatment in a stress management programme or conventional therapy which included the antispasmodic Colpermin. The stress management programme involved a median of six 40-min sessions with a physiotherapist during which patients were helped to understand the nature of their symptoms, their relationship to stress and were taught relaxation exercises. Two thirds of those in the stress management programme found the programme effective in relieving symptoms and experienced fewer attacks of less severity. This benefit was maintained for at least 12 months. Few of those given conventional management had any benefit. A stress management programme would appear to be of value for patients with irritable bowel syndrome.

Tripotassium dicitrato bismuthate enemas in the treatment of ulcerative proctitis.

Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.

Do non-steroidal anti-inflammatory drugs or smoking predispose to Helicobacter pylori infection?

Susceptibility to Helicobacter pylori infection is a poorly understood phenomenon. This study was undertaken to establish whether either smoking or chronic non-steroidal anti-inflammatory drug (NSAID) consumption might in some way predispose to H. pylori infection and hence lead to peptic ulceration. Serological evidence of H. pylori infection was assessed in 100 consecutive subjects receiving NSAIDs without any evidence of gastrointestinal upset and 100 matched controls. All subjects had a full assessment of their smoking habits. Sixty-three per cent of patients taking NSAIDs compared to 51% of controls had evidence of H. pylori infection (NS). Smoking habit also had no effect on H. pylori colonization. The ulcerogenic potential of NSAIDs and smoking does not appear to be mediated via a prediposition to H. pylori infection.

Effect of ulcerative colitis and smoking on rectal blood flow.

Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history.

Effect of nicotine and cotinine on the production of oxygen free radicals by neutrophils in smokers and non-smokers.

1. Neutrophils play a role in the pathogenesis of ulcerative colitis. Most of the patients with ulcerative colitis are non-smokers. 2. Neutrophil function was examined in healthy males, five smokers and five non-smokers, measuring production of oxygen free radicals by chemiluminescence. 3. The chemiluminescence was examined in the presence of nicotine and its main metabolite cotinine in various concentrations. 4. 10 mM nicotine inhibited production of oxygen free radicals (90.2% +/- 11.6) compared with controls (P less than 0.001), as did the same concentration of cotinine (58.9% +/- 34.2), (P less than 0.05). 5. 1 mM solutions had no effect and 3 mM nicotine was required to achieve 50% inhibition. 6. Smokers and non-smokers did not differ. 7. Since plasma concentrations of nicotine after a cigarette are only between 5 and 15 mM, the observed effects of nicotine and cotinine in much higher pharmacological concentrations in this system are unlikely to be of clinical relevance in ulcerative colitis.