[5-HT3-antagonists as a substitute for metoclopramide and domperidone: a literature review]. / 5-HT3-receptorantagonisten als vervangers van metoclopramide en domperidon.

OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts. RESULTS: In total, 56 articles were included in this review. The conclusion in 51 studies was that the efficacy of 5-HT3-antagonists in nausea and vomiting is comparable or even superior to that of metoclopramide. Metoclopramide more often caused extrapyramidal side effects; 5-HT3-antagonists were more likely to cause headaches and constipation. The majority of the studies compared metoclopramide with ondansetron. None of the articles studied palonosetron, and only one study compared domperidone with a 5-HT3-antagonist. CONCLUSION: We found enough evidence to presume that metoclopramide can be replaced by 5-HT3-antagonists for preventing delayed chemotherapy-induced nausea and vomiting and for prophylaxis or treatment of postoperative nausea and vomiting. More research is needed into the other indications and into the substitutability of domperidone.

Rapid EPA and DHA incorporation and reduced PGE2 levels after one week intervention with a medical food in cancer patients receiving radiotherapy, a randomized trial.

BACKGROUND & AIMS: In cancer patients, metabolic alterations, reduced immune competence and anti-cancer treatment can increase the risk of infections. A rapid-acting nutritional intervention might reduce this risk and support overall treatment. The present study investigated whether one week of intervention with a specific medical food led to fatty acid incorporation and functional immunological changes. METHODS: In a randomized, double-blind study, 38 cancer patients receiving radiotherapy consumed daily for one week 400 ml of specific medical food, which is high in protein and leucine, and enriched with fish oil and specific oligosaccharides (Active group), or iso-caloric/iso-nitrogenous product (Control group). Blood samples were taken at day 0 (baseline) and day 7. RESULTS: After one week of intervention, the incorporation of EPA and DHA in white blood cells was significantly higher in the Active group (2.6% and 2.6% of total fatty acids) compared to the Control group (1.0% and 2.2% of total fatty acids) (p < 0.001 and p < 0.05). Serum PGE2 levels decreased in the Active group and increased in the Control group (p < 0.01). No differences were observed on cytokine production in LPS-stimulated whole blood cultures. CONCLUSIONS: In cancer patients receiving radiotherapy, nutritional intervention with a specific medical food rapidly increased the percentage EPA and DHA in white blood cell phospholipids and reduced serum levels of the inflammatory mediator PGE2 within one week. CLINICAL REGISTRATION NUMBER: NTR2121.

Disease activity patterns in juvenile systemic lupus erythematosus and its relation to early aggressive treatment.

This study aimed to determine disease activity patterns in juvenile systemic lupus erythematosus (jSLE) and its relation to early treatment. All jSLE patients who visited the outpatient departments of three Dutch university hospitals for at least 6 months were included. Data were retrospectively collected from each patient visit and hospitalization. Patient characteristics, clinical and laboratory findings categorized in organ systems, flare rate, medication use and disease course were analysed. Included were 35 patients (female 77%; White 47%) with a total follow-up of 142 years. Median age at diagnosis was 12.8 years. Flare rate was 0.45/ patient-year. An organ system not earlier involved was affected in 34% of flares. Identifiable disease activity patterns were: chronic active (49%), relapse remitting (14%) and long quiescence (37%), with no significant difference in organ involvement at diagnosis. Positive anti-Sm and non-White ethnicity were significantly associated with a chronic active pattern. In 14 patients with severe symptoms at diagnosis, treatment with intravenous cyclophosphamide and/or biologics and/or intravenous methylprednisone in the first 6 months resulted in a long quiescence pattern in seven patients. In conclusion, distinct disease activity patterns are identifiable in children. Suppression of disease with early aggressive treatment may decrease the rate of progression.

[As-needed treatment with gastric acid inhibitors in gastroesophageal reflux disease]. / 'Zo nodig'-gebruik van zuurremmende middelen bij refluxziekte.

Although proton pump inhibitors and H2-receptor antagonists are usually prescribed for continuous use by patients with gastro-oesophageal reflux disease, at least 50% of such patients do not take their medication daily and some take it only sporadically. On-demand treatment with proton pump inhibitors or H2-receptor antagonists is safe and cost-effective. Indications are: (a) incidental reflux episodes of short duration, (b) periodic reflux lasting several weeks or months, (c) chronic reflux not requiring continuous treatment. On-demand treatment is unsuitable for patients with reflux disease who either require daily medication or in whom the maximal dosage is insufficient. There are three types of on-demand treatment. Type 1: use of medication only in case of incidental symptoms. Type 2: continuous medication for 2-4 weeks when symptoms appear. Type 3: continuous use because of chronic symptoms, but the interval between doses is determined by the patient on the basis of his symptoms. All antacids can in principle be used for on-demand treatment; for type 3 treatment, antacids with a rapid onset of action are preferred. A favourable response to the two weeks of initial therapy is a good predictor for successful on-demand treatment.

[Drug treatment of gastro-esophageal reflux disease in pregnant women: consensus guidelines of gastroenterologists and gynaecologists]. / Medicamenteuze behandeling van gastro-oesofageale refluxziekte bij zwangeren: consensusrichtlijn van gastro-enterologen en gynaecologen.

Lifestyle changes are recommended as the first step in the treatment of pregnant women with heartburn. If symptoms persist, antacids or the mucoprotective sucralfate can be prescribed. If symptoms are persistent and severe, acid secretion inhibitors may be prescribed; the proton-pump inhibitor omeprazole is the drug of choice. It is unlikely that this drug could harm the fetus but the possibility cannot be entirely excluded. Prescription should be delayed until after the first trimester, whenever possible. Patients who have become pregnant while using these drugs can be reassured.

Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome.

BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. AIM: : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. METHOD: A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. RESULTS: A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS: Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

A double-blind, randomized comparison of omeprazole Multiple Unit Pellet System (MUPS) 20 mg, lansoprazole 30 mg and pantoprazole 40 mg in symptomatic reflux oesophagitis followed by 3 months of omeprazole MUPS maintenance treatment: a Dutch multicentre trial.

BACKGROUND: Proton pump inhibitors (PPIs) have proved to be effective in treating reflux oesophagitis. Until now, no study had compared the PPIs omeprazole Multiple Unit Pellet System (MUPS), lansoprazole and pantoprazole in patients with reflux oesophagitis. AIM: To compare omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg for treatment effect in symptomatic reflux oesophagitis. METHOD: Patients with grade I-IV symptomatic reflux oesophagitis were randomized to double-blind omeprazole 20 mg once morning, lansoprazole 30 mg o.m. or pantoprazole 40 mg o.m. Patient satisfaction and symptoms were evaluated after 4 and 8 weeks. Patients not satisfied after 8 weeks were treated for another 4 weeks with omeprazole 40 mg MUPS (open). Successful treatment was followed by 3 months' maintenance treatment with omeprazole MUPS 20 mg (patients satisfied after 4 or 8 weeks) or omeprazole MUPS 40 mg (patients satisfied after 12 weeks). RESULTS: On intention-to-treat (ITT) analysis (n = 461) at 4 and 8 weeks, respectively, 84% and 87% (omeprazole MUPS), 78% and 81% (lansoprazole), and 84% and 89% (pantoprazole) were free of heartburn. Equivalence was found between omeprazole MUPS and pantoprazole (heartburn relief), but not with lansoprazole. Patient satisfaction after 4 and 8 weeks, respectively, was 79% and 89% (omeprazole MUPS), 76% and 86% (lansoprazole), and 79% and 91% (pantoprazole). Patient satisfaction was similar in all treatment groups. During maintenance, 87% in the omeprazole MUPS 20 mg group and 81% in the omeprazole MUPS 40 mg group were satisfied after 3 months. CONCLUSIONS: Omeprazole MUPS 20 mg and pantoprazole 40 mg have equivalent efficacy in the treatment of reflux oesophagitis. Based on patient satisfaction, omeprazole MUPS 20 mg, lansoprazole 30 mg and pantoprazole 40 mg are equally effective.

Impact of injections during diagnostic coronary arteriography on coronary patency in the setting of acute myocardial infarction from the TIMI trials. Thrombolysis In Myocardial Infarction.

The mechanical force of injection at 90 minutes opens 13.4% of occluded arteries, but overall, only 2.4% of all culprit arteries (already open and occluded combined) are opened. Thus, although some arteries are opened by the force of hand injection, the frequency of mechanical opening among all arteries is low, and hand injections appear to alter current 80% patency rates by approximately 2.5%.

Relief of dyspeptic symptoms by colloidal bismuth subcitrate in Helicobacter-negative and -positive patients: results of a study in general practice.

BACKGROUND: The role of H. pylori in non-ulcer dyspepsia is controversial. Colloidal bismuth subcitrate (CBS) is known to suppress H. pylori. We hypothesized that if H. pylori is a causal factor in dyspepsia, then suppression of H. pylori would lead to a decrease in symptoms. AIM: To assess the relationship between H. pylori status and the effect of CBS on dyspeptic symptoms in patients visiting their general practitioner for dyspeptic complaints. METHODS: In total 446 patients between 17 and 81 years of age (median 44 years) were included. All patients were treated with CBS (240 mg Bi2O3) twice a day for 4 weeks. Symptoms were scored at baseline, and after 2 and 4 weeks of treatment. At the first visit, blood was taken for serological H. pylori testing. RESULTS: During follow up, 65 patients were lost due to violation of protocol. Positive H. pylori serology was found in 110 (24.7%) of the 446 initially selected patients, and in 90 (23.6%) of the 381 patients who completed the protocol (NS). The mean overall symptom score decreased significantly after 4 weeks of CBS (P<0.001). This reduction in overall symptom score was not significantly different between the H. pylori-positive and -negative groups. CONCLUSIONS: The H. pylori status does not influence the outcome of CBS therapy in patients who consult their general practitioner for dyspepsia. This finding suggests that H. pylori does not play an important role in the etiology of dyspepsia in patients seen by the general practitioner.

[Meperidine (pethidine) outdated as analgesic in acute pancreatitis]. / Pethidine achterhaald als pijnstiller bij acute pancreatitis.

The most important symptom in acute pancreatitis is pain. This pain often is so severe that treatment is started with opioid analgesics. In daily practice meperidine is often the analgesic of first choice because it is supposed to cause less spasm of the M. sphincter ampullae hepatopancreaticae (sphincter of Oddi). Drawbacks of the use of meperidine compared with other opiods are myoclonias, tremors and convulsions due to accumulation of the metabolite norpethidine, and hypotension, tachycardia and erythema due to release of more histamine from mast cells. From literature study it appeared that all opioids have a spasmogenic effect on the sphincter of Oddi, that there are no good arguments to assume that this effect is less when meperidine is used, and that there is no good evidence that this spasmogenic effect of opioid analgesics influences the course of acute pancreatitis in an unfavourable way. Since the profile of effects and side effects of meperidine is unfavourable, we prefer the use of opioids with a larger therapeutic width.

[Intestinal infections due to inhibition of gastric acid secretion in reflux disease]. / Intestinale infecties door maagzuursecretieremming bij refluxklachten.

Gastric acid stimulates the absorption of nutrients and is the most important non-immunological defence system against the constant bacterial invasion of our digestive tract. Patients with achlorhydria and resected stomachs have excessive growth of bacteria in the digestive tract and a much higher incidence of gastrointestinal infections. Modern treatment of reflux oesophagitis with acid secretion inhibitors creates a similar low acid state. Suppression of gastric acid secretion causes a dose dependent increased risk of a wide variety of intestinal infections especially for people over 65, immune compromised persons, sick patients with a reduced resistance and travellers to tropical areas. The potentially dangerous infections can be reduced by adequate counselling about the importance of gastric acid, the precaution of improved hygiene, on demand use of especially proton pump inhibitors and prescription of antacids and less potent acid inhibitors.

Optimal treatment of Helicobacter pylori with ranitidine bismuth citrate (RBC): a randomized comparison between two 7-day triple therapies and a 14-day dual therapy.

OBJECTIVE: We investigated two promising 1-wk RBC-triple therapies in comparison to the already well investigated 2-wk RBC dual therapy. METHODS: We conducted two randomized, open, parallel group studies in 13 hospitals in the Netherlands. H. pylori-positive patients without active ulceration were randomized to 14-day RBC 400 mg b.i.d. plus clarithromycin 500 mg b.i.d. (n = 56) or to either 7-day RBC 400 mg b.i.d. plus tetracycline 500 mg q.i.d. plus metronidazole 500 mg t.i.d. (n = 63) in study 1, or to 7-day RBC 400 mg b.i.d. plus amoxycillin 1000 mg b.i.d. plus clarithromycin 500 mg b.i.d. (n = 49) in study 2. At least 6 wk later patients were reendoscoped with antral and corpus biopsies for CLOtest, culture, and histology, and cure was assumed if all tests were negative. RESULTS: Results from the studies were pooled. All regimens were well tolerated with only 1 drop-out because of side effects. Cure rates per protocol/intention to treat were 96%/95% for RBC-CLA dual therapy, 89%/86% for RBC-TET-MET triple therapy, and 93%/92% for RBC-AMO-CLA triple therapy. From 126 patients, a pretreatment antibiogram was available. Metronidazole resistance did not affect the performance of RBC-CLA or RBC-AMO-CLA. In the RBC-TET-MET group, 97% (32/33) with a metronidazole sensitive strain were cured vs 57% (four of seven) with a resistant strain. Of three patients with a pretreatment clarithromycin resistant strain; one failed RBC-CLA dual therapy and two failed RBC-AMO-CLA triple therapy. CONCLUSIONS: All regimens were well tolerated and achieved comparable and very high cure rates. Statistical or clinical relevant differences were not detected. All three regimens can be used as initial anti-Helicobacter therapy and can compete with 7-day PPI-triple therapies. More data are needed on the influence of antimicrobial resistance on the performance of individual triple therapies. The local prevalence of antimicrobial resistance will determine which regimen should be chosen for a certain geographical area.

Colonic spread of 5-ASA enemas in healthy individuals, with a comparison of their physical and chemical characteristics.

BACKGROUND: 5-aminosalicylic acid (5-ASA) is widely used as topical treatment in patients with distal inflammatory bowel disease. The enema spread and retention time are considered to be important factors in the efficacy of this therapeutic agent. Whereas colonic spread is widely investigated in selected patient populations and volunteers, much less attention has been given to the in vitro differences of physical and chemical properties, although they may influence the in vivo characteristics. METHODS: Two different brand enemas, Salofalk and Asacol, both containing 2 g mesalazine, were compared with respect to their in vivo and in vitro characteristics. The retrograde spread, maximum distribution and wall adhesion, as well as the retention time of the enemas, was examined by the addition of a technetium tracer dose in 12 healthy volunteers on two separate occasions. In addition, several chemical properties such as pH, viscosity, particle size, dispersion rate, specific surface area and residual volume after application were analysed and compared. RESULTS: With its larger volume and higher viscosity the Asacol preparation reached a substantially larger proportion of the colon and produced a significantly higher retention time in the proximal parts of the large intestine. In addition, more than double the amount of 5-aminosalicylic acid was not expelled from the semi-rigid Salofalk enema container after application. With respect to chemical properties it was demonstrated that the Asacol preparation showed a significantly smaller size of micronized 5-aminosalicylic acid particles, better homogeneity and much less aggregation of the drug. This resulted in an almost threefold higher specific surface area per g active compound. CONCLUSIONS: The Asacol enema appears to be superior in several aspects of the galenical formulation. The better dispersion and larger specific surface area, in conjunction with a larger distribution, better bowel wall adherence and retention time in vivo, constitute a clear theoretical and possible clinical advantage.

Two different dose regimens of cisapride in the treatment of reflux oesophagitis: a double-blind comparison with ranitidine.

We conducted a double-blind study comparing two dosage regimens of a prokinetic drug, cisapride (10 mg q.d.s. and 20 mg b.d.), with a low dose of a H2-receptor antagonist (150 mg ranitidine b.d.) in the treatment of 155 patients with reflux oesophagitis as determined by endoscopy. The active treatment took 8 to 12 weeks depending on whether complete healing was found at endoscopy. Improvement in oesophagitis grades from baseline to endpoint was observed in 68% of patients in the 10 mg cisapride q.d.s. group, 83% in the cisapride 20 mg b.d. group and 81% in the ranitidine group (N.S.). At endpoint, the percentages of endoscopically cured patients with initial grades I or II were 52% for 10 mg cisapride q.d.s., 71% for 20 mg cisapride b.d. and 80% for ranitidine (N.S.). The proportional improvement of the overall reflux symptom score (60%) also showed no significant difference between the three groups. In the treatment of mild reflux oesophagitis (grades I and II) similar results can be expected from 20 mg cisapride b.d. and 150 mg ranitidine b.d. As the results of the two dosage regimens of cisapride were not different, the 20 mg twice daily regimen is preferred because it will improve patient compliance. It is concluded that in reflux oesophagitis grades I and II, the efficacy of 20 mg cisapride b.d. and 150 mg ranitidine b.d. are broadly similar.

Intramural hematoma of the esophagus caused by minor head injury 6 hours previously.

The diagnosis of extensive intramural hematoma of the esophagus due to a bicycle trauma was considerably delayed because symptoms did not develop until 6 h after the accident. This report underscores the importance of a barium meal and computed tomographic (CT) scan in cases of unexplained chest pain, even after minor trauma.

Metabolism of triiodothyronine in rat hepatocytes.

The metabolism of T3 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, HPLC, and RIA for T3 sulfate (T3S) and 3,3'-diiodothyronine (3,3'-T2). Type I iodothyronine deiodinase activity was inhibited with propylthiouracil (PTU), and phenol sulfotransferase activity by SO4(2-) depletion or with competitive substrates or inhibitors. Under normal conditions, labeled T3 glucuronide and I- were the main products of [3'-125I]T3 metabolism. Iodide production was decreased by inhibition (PTU) or saturation (greater than 100 nM T3) of type I deiodinase, which was accompanied by the accumulation of T3S and 3,3'-T2S. Inhibition of phenol sulfotransferase resulted in decreased iodide production, which was associated with an accumulation of 3,3'-T2 and 3,3'-T2 glucuronide, independent of PTU. Formation of 3,3'-T2 and its conjugates was only observed at T3 substrate concentrations below 10 nM. Thus, T3 is metabolized in rat liver cells by three quantitatively important pathways: glucuronidation, sulfation, and direct inner ring deiodination. Whereas T3 glucuronide is not further metabolized in the cultures, T3S is rapidly deiodinated by the type I enzyme. As confirmed by incubations with isolated rat liver microsomes, direct inner ring deiodination of T3 is largely mediated by a low Km, PTU-insensitive, type III-like iodothyronine deiodinase, and production of 3,3'-T2 is only observed if its rapid sulfation is prevented.