Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.

Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review.

B-cell-activating factor (BAFF) influences peripheral B-cell survival, maturation and immunoglobulin class-switch recombination and has a range of potential clinical implications. Biological functions of BAFF and its relevance in various clinical disorders including currently investigated BAFF-targeting therapies are reviewed and discussed based on PubMed search of relevant articles. Serum levels of BAFF are increased in autoimmune diseases including autoimmune hepatitis and primary biliary cirrhosis where BAFF concentrations are related to titres of autoantibodies and disease progression. Increased BAFF levels are found in synovial, bronchoalveolar and gut lavage fluids, suggesting local class switching and immunoglobulin production. Clinical relevance and diagnostic potential of BAFF are also noted in patients with allergic diseases, malignancies and infections including hepatitis C virus. BAFF antagonists are promising new therapeutic agents, currently being tried in B-cell-related autoimmune diseases. Serum level of BAFF may indicate disease mechanisms and the degree of activity. Determination of BAFF in different body compartments like synovium, airways and gut may also have clinical implications. Results of ongoing clinical trials with BAFF antagonists are eagerly awaited.

Job stress and coping strategies in patients with subjective food hypersensitivity.

Psychological distress may be causally related to multiple, unexplained somatic symptoms. We have investigated job stress, coping strategies and subjective health complaints in patients with subjective food hypersensitivity. Sixty-four patients were compared with 65 controls. All participants filled in questionnaires focusing on job stress, job demands and control, work environment, coping strategies and subjective health complaints. Compared with controls, patients scored significantly lower on job stress and job demands, and significantly higher on authority over job decisions. Coping strategies and satisfaction with work environment did not differ significantly between the two groups, but the patients reported significantly more subjective health complaints than the controls. Scores on job stress and job demands were generally low in patients with subjective food hypersensitivity. It is unlikely, therefore, that the patients' high scores on subjective health complaints are causally related to the work situation.

White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels.

OBJECTIVE: To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. MATERIAL AND METHODS: 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. RESULTS: WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. CONCLUSIONS: WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.

Distension-induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation.

Functional dyspepsia (FD) is associated with impaired gastric accommodation and autonomic dysregulation. The aim of this study was to investigate the effects of autonomic manipulation on distension-induced gastric accommodation in subjects with and without FD, using a newly developed gastric barostat paradigm. Twelve healthy subjects (HS) and 18 subjects with FD had four barostat examinations each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental relaxation with deep breathing) and acute stress stimulation (serial subtraction task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed using predefined parameters. There were no significant group differences in accommodation variables between HS and subjects with FD. The FD group could be subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11). In subgroup 1, but not in subgroup 2 atropine increased maximum volume and accommodation rate substantially. Neither mental stress nor mental relaxation changed any of the accommodation variables. In a subgroup of subjects with FD, impairment of distension-induced gastric accommodation can be improved by cholinergic blockade, but not by acute physiological autonomic manipulation.

Effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease.

BACKGROUND: Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species. AIM: To compare the effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease. METHODS: Forty-one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron-polymaltose complex 200 mg once a day for 14 days. RESULTS: Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not change significantly. Iron-polymaltose complex did not change plasma malondialdehyde, urine 8-isoprostaglandin F(2alpha) or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not differ. Neither ferrous sulphate nor iron-polymaltose complex altered clinical disease activity indices. CONCLUSIONS: Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron-polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.

Bacteria-derived particles as adjuvants for non-replicating nasal vaccines.

In attempts to mimic natural infections, vaccines consisting of microbial particles may be delivered directly to mucosal surfaces. In this way, the mucosal as well as the systemic immune systems can be activated. Even non-living particles of bacterial origin have been shown to elicit strong immune responses when administered intranasally. However, some particles such as formalin-inactivated influenza virus may need a mucosal adjuvant to be effective. The bacteria-derived particles seem to possess such an adjuvant activity when mixed with and given intranasally with the less immunogenic killed virus. Possibly, the bacterial particles facilitate uptake of the virus through the mucosal membranes, although an additional influence on the immune response to the virus might be mediated in the lymphoid tissue below the mucosal surface. Bacteria-derived particles in nasal vaccines may thus serve as an alternative adjuvant to derivatives of cholera toxin or the heat-labile toxin from E. coli.

Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) is a very common disorder of upper gastro-intestinal motility, differing widely in severity and prognosis. Medical therapy of GORD has involved antacids, alginates, prokinetic agents and antisecretory compounds, primarily H2 receptor antagonists and proton pump inhibitors. Knowledge of the pharmacokinetics of these compounds is important, to optimise the therapeutic benefit in each patient. GORD patients are often elderly and pharmacokinetics are move variable in this group. Furthermore, they often suffer from other diseases needing medical therapy and may need a combination of drugs to heal reflux oesophagitis and relieve reflux symptoms. The ideal therapy for GORD will have linear pharmacokinetics, a relatively long plasma half-life (t1/2), a duration of action allowing once daily administration, and a stable effect independent of interactions with food, antacids and other drugs. Over-the-counter antacids and alginates are widely used, buy may affect absorption of H2 receptor antagonists like cimetidine and ranitidine. Aluminium-containing antacids may, over time, cause toxicity in patients with renal insufficiency. In the treatment of GORD, cisapride presents important advantages over earlier prokinetic compounds, with a longer plasma t1/2, low penetration of the blood-brain barrier and fewer adverse effects. The group of H2 receptor antagonists is still the most frequently use therapy for GORD. Linear pharmacokinetics make dose adjustments easy and safe. In individual patients, suppression of gastric secretion is related to the area under the plasma concentration-time curve (AUC), but there is wide interindividual variation in the effect of the same oral dose. Only with frequent administration and high doses will acid suppression approximate that of proton pump inhibitors. Tolerance, with loss of effect over time, however, is most pronounced in this situation. H2 receptor antagonists seem well suited for on-demand treatment of reflux symptoms, due to the rapid onset of effect and a decrease likelihood of the development of tolerance. Effervescent formulations provide more rapid absorption and almost immediate clinical effect. Cimetidine, however, causes interference with the metabolism of several other drugs in common use. In elderly patients elimination is delayed and in patients with renal insufficiency, dose reductions of all H2 receptor antagonists are recommended. The most effective medical therapy for any severity of GORD, particularly in severe oesophagitis, are the proton pump inhibitors. The substituted benzimidazoles (omeprazole, lansoprazole and pantoprazole), are prodrugs which once trapped and activated in the acid milieu of the gastric glands potently suppress gastric secretion of acid and pepsin. Their long duration of action, more related to the slow turnover of parietal cell H(+)-K+ ATPase molecules, allows once daily administration in most patients. Interindividual variation in bioavailability sometimes calls for higher doses or twice daily administration. Acid suppression is closely related to the AUC. Omeprazole is prone to interaction with the metabolism of other drugs, some of which may e be clinically important. Lansoprazole seems to have an earlier onset of action than omeprazole, ascribed to higher bioavailability during the first days of treatment. Proton pump inhibitors have a slow onset of action, which makes them unsuited for on-demand therapy. Clinical practice in GORD calls for the use of not one but several substances, according to the severity and symptom pattern of the patient. Pharmacokinetic optimisation in the treatment of GORD is a question of selecting the most suitable substances and administration schemes within each group. Cisapride is superior to other prokinetics in terms of longer plasma t1/2 and less toxicity. Amongst H2 receptor antagonists, the more long-acting compounds, ranitidine and famotidine, will improve acidity control througho

Effect of enprostil on basal and meal-stimulated gastric acid and pepsin secretion, serum gastrin and gastric emptying in healthy persons.

Ten healthy volunteers took part in a double-blind, randomized, cross-over study of the effect of single doses of enprostil (70 micrograms) and placebo on basal and meal-stimulated gastric acid, pepsin secretion and serum gastrin. Meal-stimulation was induced by modified sham feeding combined with repeated gastric instillation and withdrawal of meat soup. When studied between 1 and 2.5 hours after oral administration of the drug, enprostil decreased basal acid output by 92% (P less than 0.001) and stimulated acid output by 70% (P less than 0.001). Basal and stimulated volumes of gastric juice were decreased by 50% (P less than 0.02) and 35% (P less than 0.002), respectively. Enprostil decreased stimulated pepsin output by 34% (P less than 0.05), but had no effect on the concentration of pepsin. Neither basal nor stimulated serum gastrin concentrations were affected by enprostil. Percent recovery of the meal was measured by an unabsorbable marker, polyethylene glycol, instilled into the stomach mixed with the soup. Polyethylene glycol recovery decreased from 89% with placebo to 67% with enprostil (P less than 0.01), indicating an enhanced gastric emptying rate with enprostil.

Lansoprazole 15 and 30 mg daily in maintaining healing and symptom relief in patients with reflux oesophagitis.

BACKGROUND: In patients with reflux oesophagitis, endoscopic healing and symptom relief are considered important treatment goals in long-term care. AIM: To compare the effect of lansoprazole 15 and 30 mg daily on maintaining endoscopic healing and symptom relief in patients with moderate reflux oesophagitis. PATIENTS AND METHODS: In a single-centre, double-blind randomized clinical trial, 103 patients with grade 1 or 2 reflux oesophagitis who were endoscopically healed and asymptomatic after lansoprazole 30 mg daily for 12 weeks, were randomized to maintenance therapy with either lansoprazole 15 mg or 30 mg o.m. Endoscopy was repeated after 3, 6 and 12 months, and symptom relief assessed after 3, 6, 9 and 12 months. Relapse of oesophagitis or symptoms were considered end-points. RESULTS: After 12 months, 14/50 patients (28%) receiving lansoprazole 15 mg daily had suffered an endoscopic relapse compared to 8/53 patients (15%) treated with lansoprazole 30 mg daily. A life table analysis showed no statistically significant difference between the two groups (P = 0.086). Significantly more patients were kept in complete symptomatic remission in the 30 mg group (P < 0.01). In the 15 mg group, 23/50 (46%) had suffered either an endoscopic or symptomatic relapse on completion of the study, compared to 12/53 (23%) in the 30 mg group. A life table analysis showed this difference to be statistically significant (P = 0.010). Lansoprazole 15 and 30 mg daily were equally well tolerated. CONCLUSION: No statistically significant differences were found in endoscopic relapse rate or occurrence of adverse events, while lansoprazole 30 mg proved superior to 15 mg in maintaining patients in symptomatic relief and combined endoscopic and symptomatic remission.

Phospholipase A2 activity in gastric juice from patients with active and H. pylori-eradicated healed duodenal ulcer.

BACKGROUND: Despite the close association between gastric Helicobacter pylori infection and duodenal ulcer, little is known about how this organism may promote mucosal damage. A possibility might be that it produces, or induces the host to release, phospholipases that metabolize the protective layer of phospholipids. METHODS: Aimed at determination of phospholipase A2 activity and the concentration of choline-containing phospholipids in gastric juice, aspirates were collected during gastroscopy in 38 consecutive referrals with either active (n = 19) or H. pylori-eradicated healed duodenal ulcer (n = 19). RESULTS: Gastric juice phospholipase A2 activity was 3.1 times higher in active than in healed duodenal ulcers (P = 0.03). Concurrently, the concentration of choline-containing phospholipids in the group with active ulcers was less than half compared with the healed group (P = 0.02). CONCLUSION: The results indicate that phospholipase A2 activity and the concentration of choline-containing phospholipids in gastric juice are related to H. pylori status and duodenal ulcer disease.

Lansoprazole in the treatment of reflux oesophagitis: a survey of clinical studies.

The newly developed proton pump inhibitor lansoprazole has been compared to placebo, ranitidine and with omeprazole in a number of clinical studies in patients with reflux oesophagitis. In three comparative studies against ranitidine, lansoprazole was found to be superior in terms of healing rates and symptom relief. In two studies against omeprazole, no significant difference was found in healing rates, while a Scandinavian study demonstrated more prompt relief from heartburn. Further studies are presently being conducted to evaluate the potential of lansoprazole in long-term treatment of reflux oesophagitis. It is concluded that lansoprazole is a safe, effective therapy for reflux oesophagitis, superior to ranitidine and comparable with omeprazole.

Prognostic factors for relapse of reflux oesophagitis and symptoms during 12 months of therapy with lansoprazole.

BACKGROUND: Symptom relief and endoscopic healing are both important treatment goals in patients with reflux oesophagitis. Knowledge of predictive factors for treatment success could facilitate choice of treatment in individual patients. AIM: To assess the value of clinical data and data from baseline ancillary investigations in predicting the outcome of maintenance therapy with a proton pump inhibitor. METHODS: After healing and symptom relief had been obtained on open therapy with lansoprazole 30 mg daily, 103 patients with reflux oesophagitis grade 1 or 2 were randomized to maintenance therapy with lansoprazole 15 or 30 mg daily, and time until recurrence of symptoms and/or endoscopic changes was recorded. The predictive value of the following variables was assessed by Cox regression analysis: dose of lansoprazole, symptom severity, grade of reflux oesophagitis. Helicobacter pylori infection status, lower oesophageal sphincter resting tone, percentage of 24 h with an oesophageal pH of <4.0, and median 24 h intragastric pH before start of treatment. RESULTS: Dose of lansoprazole (P = 0.01) and symptom severity (P < 0.05) both significantly predicted time to relapse. Grade of reflux oesophagitis had only a borderline predictive value (P = 0.09), while H. pylori infection status and data from manometry and intraoesophageal 24-hour pH-metry did not predict relapse. CONCLUSIONS: Symptom severity before starting therapy is a significant predictive factor for treatment success during potent antisecretory therapy with lansoprazole, more so than endoscopic grade of reflux oesophagitis. In a group of patients with uncomplicated reflux oesophagitis being considered for maintenance therapy with lansoprazole, ancillary investigations with endoscopy, manometry and 24-hour pH-metry gave very limited prognostic information. H. pylori infected patients relapsed as early as patients who were not infected.

The effect of Helicobacter pylori eradication on gastro-oesophageal reflux.

BACKGROUND: Increased prevalence of oesophagitis has been reported following eradication of Helicobacter pylori. We hypothesized that H. pylori eradication might increase gastro-oesophageal acid reflux in patients with reflux oesophagitis. METHODS: Twenty-five consecutive patients (13 male, 12 female) with H. pylori infection and reflux oesophagitis grade I (22 patients) or II (three patients) were enrolled; mean age 49.9 (range 33-75) years. Twenty-four hour intra-oesophageal pH recording was performed before and 12 weeks after eradication of H. pylori, which was achieved using bismuth subnitrate suspension 150 mg q.d.s., oxytetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s. for 10 days. Eradication was confirmed by 14C-urea breath test 12 weeks after completion of treatment. The patients did not receive acid-suppressive medication. RESULTS: All patients had abnormal gastro-oesophageal reflux before anti-H. pylori treatment. After treatment, there was no significant change in the percentage of total time oesophageal pH < 4 (P=0.46) in the 23 patients in whom the infection had been cured. Nine of the cured patients had increased acid exposure, whereas 14 had decreased acid exposure. No significant change in reflux symptom scores was found. There was no relationship between change in acid exposure and symptom improvement. CONCLUSIONS: Twelve weeks after H. pylori eradication there was no consistent change in gastro-oesophageal acid reflux in patients with mild or moderate reflux oesophagitis.

Acute damage of gastroduodenal mucosa by acetylsalicylic acid: no prolonged protection by antacids.

Twenty healthy volunteers participated in a double-blind, crossover study to evaluate endoscopically whether low-dose antacids have any prolonged and pH-independent protective capacity against gastroduodenal mucosal damage induced by acetylsalicylic acid. Antacid or placebo one tablet q.d.s. was given for 1.5 days. Acetylsalicylic acid (1.5 g) was administered 3 h after the last dose of antacid/placebo, and gastroscopy was performed 1 h thereafter. Thirteen of 20 subjects showed a decrease in total damage with antacids as compared with placebo, but the difference did not reach statistical significance. Thus, protection by antacids against acetylsalicylic acid-induced gastric mucosal lesions could not be documented at a time when intragastric pH presumably had returned to normal.

On demand therapy of reflux oesophagitis--a prospective study of symptoms, patient satisfaction and quality of life.

BACKGROUND: In patients with low-grade reflux oesophagitis adequate symptom control is the aim of treatment. Effervescent tablets alleviate heartburn more rapidly than ordinary tablets. AIM: To investigate symptom control, patient satisfaction, health-related quality of life and disease progress when ranitidine 150 mg effervescent tablets were offered as on demand treatment. We also wanted to investigate whether any biological or psycho-social factor could predict patient satisfaction. METHOD: Consecutive patients with endoscopically verified reflux oesophagitis grade I-II were followed up for 12 months. 24 h pH-metry, disease history, symptoms and several psycho-social factors were registered at baseline and 12 months follow-up. RESULTS: Eighty-one patients were included. Mean age was 50.7 years (range 21-82), 63% were men. Mean tablet consumption was 1.21 per day (range 7-1016 tablets/year). At the 1-year follow-up discomfort resulting from reflux symptoms was significantly reduced (P<0.001), and the patients' social and vocational life improved. Eighty-four percentage of the patients were satisfied with the treatment. 24 h pH-metry or number of reflux episodes did not change. We did not find any factors able to predict patient satisfaction. CONCLUSIONS: On demand therapy with ranitidine effervescent tablets was well accepted by the majority of patients with reflux oesophagitis grade I. Even though the number of reflux episodes did not change, the patients experienced less discomfort due to reflux symptoms, and their social and vocational life was better. There was no significant progression of the disorder during the 1-year follow-up. No predictive factor for patient satisfaction was found.

Spiramycin in triple therapy of Helicobacter pylori-associated peptic ulcer disease. An open pilot study with 12-month follow-up.

BACKGROUND: Spiramycin (Rovamycin) is a well-established macrolide antibiotic with good anti-Helicobacter pylori activity in vitro. It is acid-stable and found in high concentration in various body fluids and cells after oral administration. Its anti-H. pylori activity in vivo has not yet been tested. METHODS: Twenty-five consecutive patients with endoscopically verified peptic ulcer and a positive biopsy urease test were given spiramycin tables 1.5 MIU instead of oxytetracycline 500 mg q.d.s. in our triple therapy regimen with bismuth subnitrate suspension 10 mL (150 mg bismuth subnitrate) q.d.s. and metronidazole 400 mg t.d.s. for 10 days. Bismuth was taken between meals and spiramycin and metronidazole with meals. Re-endoscopy and 14C-urea breath test were performed 4 weeks after completion of therapy. Those who were H. pylori negative according to the breath test returned for 1-year follow-up. RESULTS: Per protocol analysis at 4 weeks showed that 21 out of 23 patients were H. pylori negative and had healed ulcers. These 21 patients were persistingly H. pylori negative and had no ulcers at 1-year follow-up. H. pylori eradication and ulcer healing rates were thus 91.3%; 95% confidence interval from 72.0% to 98.9%. Side-effects limiting daily activity were significantly less frequent than we have experienced previously using oxytetracycline in triple therapy. CONCLUSIONS: Spiramycin appears to be an alternative to tetracycline in the triple therapy of H. pylori infection. Further studies to position spiramycin as an anti-H. pylori drug are warranted.

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. AIMS: To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. RESULTS: The panel recommended antacids 'on-demand' as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. CONCLUSIONS: The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole.

BACKGROUND: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline. AIM: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin. METHODS: One hundred and eighty-three patients were randomized to one of four 10-day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C-urea breath test was performed at 8 weeks. RESULTS: Intention-to-treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex-smokers (93%) and smokers (89%) (P = 0.06). Fifty-three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002). CONCLUSIONS: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.

A nasal whole-cell pertussis vaccine induces specific systemic and cross-reactive mucosal antibody responses in human volunteers.

A whole-cell pertussis vaccine, each dose consisting of 250 microg of protein, was given intranasally four times at weekly intervals to six adult volunteers. All vaccinees responded with increases in nasal fluid IgA antibodies to Bordetella pertussis whole-cell antigen. Three vaccinees with high nasal antibody responses also developed increased serum IgA and IgG antibodies to this antigen. Salivary antibody responses to the whole-cell antigen, as well as antibodies in serum and secretions to pertussis toxin (PT) and filamentous haemagglutinin (FHA) were negligible, except for a moderate increase in nasal fluid antibodies to FHA. Unexpectedly, the same vaccinees developed significant rises in nasal and salivary IgA antibodies to meningococcal outer-membrane antigens, whereas corresponding serum IgA and IgG antibodies were unchanged. Thus it appears that mucosal immunisation may induce secretory antibodies with broader specificities than can be found in serum.