New perspectives in the prediction of postoperative complications for high-risk ulcerative colitis patients: machine learning preliminary approach.

OBJECTIVE: Patients with acute severe and medical refractory ulcerative colitis have a high risk of postoperative complications after total abdominal colectomy (TAC). The objective of this retrospective study is to use machine learning to analyze and predict short-term outcomes. PATIENTS AND METHODS: 32 patients with ulcerative colitis were treated with total abdominal colectomy between 2011 and 2017. Biographical data, preoperative therapy, blood chemistry, nutritional status, surgical technique, blood transfusion and preoperative length of stay were the features selected for the statistical analyses and were used as input for the machine learning algorithms to predict the rate of complications. RESULTS: Traditional statistical analysis showed an overall postoperative morbidity rate of 34% and a mortality rate of 3%. Preoperative low serum albumin levels (<2.5 g/dL) were related to a higher risk of minor infectious complications with statistical significance (p<0.05). Preoperative length of stay (>4 days), blood transfusions (≥1 unit) and body temperature (≥37.5°C) demonstrated a major impact on infectious morbidity with statistical significance (p<0.05). Patients treated with steroids and rescue therapy presented a higher risk of minor infectious complications (p<0.05). Evaluating only preoperative features, machine learning algorithms were able to predict minor postoperative complications with a high strike rate (84.3%), high sensitivity (87.5%) and high specificity (83.3%) during the testing phase. CONCLUSIONS: Machine learning is demonstrated to be useful in predicting the rate of minor postoperative complications in high-risk ulcerative colitis patients, despite the small sample size. It represents a major step forward in data analysis by implementing a retrospective study from a prospective point of view.

Inhibition of the SH3 domain-mediated binding of Src to the androgen receptor and its effect on tumor growth.

In human mammary and prostate cancer cells, steroid hormones or epidermal growth factor (EGF) trigger association of the androgen receptor (AR)-estradiol receptor (ER) (alpha or beta) complex with Src. This interaction activates Src and affects the G1 to S cell cycle progression. In this report, we identify the sequence responsible for the AR/Src interaction and describe a 10 amino-acid peptide that inhibits this interaction. Treatment of the human prostate or mammary cancer cells (LNCaP or MCF-7, respectively) with nanomolar concentrations of this peptide inhibits the androgen- or estradiol-induced association between the AR or the ER and Src the Src/Erk pathway activation, cyclin D1 expression and DNA synthesis, without interfering in the receptor-dependent transcriptional activity. Similarly, the peptide prevents the S phase entry of LNCaP and MCF-7 cells treated with EGF as well as mouse embryo fibroblasts stimulated with androgen or EGF. Interestingly, the peptide does not inhibit the S phase entry and cytoskeletal changes induced by EGF or serum treatment of AR-negative prostate cancer cell lines. The peptide is the first example of a specific inhibitor of steroid receptor-dependent signal transducing activity. The importance of these results is highlighted by the finding that the peptide strongly inhibits the growth of LNCaP xenografts established in nude mice.

Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy.

We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related.

Effects of ranitidine bismuth citrate on gastric acid secretion and gastrin release in subjects with and without Helicobacter pylori infection.

BACKGROUND: Ranitidine bismuth citrate is a novel antiulcerant that provides the antisecretory activity of ranitidine and the gastric mucosal protection and antibacterial properties of bismuth. METHODS: This randomized, double-blind, placebo-controlled study evaluated the effects of single doses of ranitidine bismuth citrate 200 mg, 400 mg and 800 mg and ranitidine hydrochloride 150 mg on gastrin release and suppression of gastric acid secretion, and compared acid secretory profiles and gastrin release between Helicobacter pylori-negative and -positive patients. Plasma gastrin concentrations were determined by radioimmunoassay under basal conditions and in response to peptone meal stimulation. Acid secretion was measured under basal conditions and in response to peptone meal stimulation. Presence of H. pylori was determined by both 14C-urea breath test and ELISA serology. RESULTS: Inhibition of gastric acid output by ranitidine bismuth citrate was both time- and dose-dependent over the 9-h post-dose study period. Doses of ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg, which are equimolar, produced similar suppression of acid output regardless of H. pylori status. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations regardless of H. pylori status. All doses of ranitidine bismuth citrate were well tolerated. CONCLUSIONS: Ranitidine bismuth citrate caused time- and dose-dependent reductions in meal-stimulated and between-meal gastric acid output regardless of H. pylori status. The magnitude of decreased acid secretion was similar with ranitidine bismuth citrate 400 mg and ranitidine hydrochloride 150 mg. Ranitidine bismuth citrate had no effect on plasma gastrin concentrations.

Determination of the time of onset of action of ranitidine and famotidine on intra-gastric acidity.

BACKGROUND: No standard methods exist for determining the onset of action of gastric antisecretory agents in human subjects. METHODS: Intragastric pH was measured when placebo, ranitidine 150 mg, ranitidine 75 mg or famotidine 10 mg were administered 30 min after the end of a meal. RESULTS: When the onset of action was defined as the earliest time that mean gastric pH with active treatment was statistically significantly higher (P < 0.05) than the corresponding placebo value, the onsets of action of ranitidine 75 mg and 150 mg were 55 min, and of famotidine 10 mg, 90 min. When onset was defined in terms of a particular decrease in gastric acid concentration for the group as a whole or for individual subjects, there was an important variation in the relative times of onset of ranitidine 75 mg and famotidine 10 mg. CONCLUSIONS: When administered after a meal, the onset of action of ranitidine and famotidine on gastric pH can be determined for individual subjects as well as for the group as a whole. When onset was determined for the group using statistical significance, which does not depend on arbitrary cut-off points, ranitidine 75 mg had an earlier onset of action than did famotidine 10 mg.

A single dose of ranitidine 150 mg modulates oesophageal acid sensitivity in patients with functional heartburn.

BACKGROUND: The rapid onset and symptomatic response to histamine-2 receptor antagonists prior to the pharmacological effect on acid secretion suggests a different mechanism of action. AIM: To determine if ranitidine decreases oesophageal sensitivity to chemical and mechanical stimulation, potentially via oesophageal histamine receptors. METHODS: A total of 18 patients with functional heartburn received oral ranitidine 150 mg b.d. or placebo for 7 consecutive days in a double-blind randomized crossover design and underwent Barostat balloon distention and Bernstein acid infusion on study day 1 (90 min postdose) and study day 7. First sensation and pain were recorded and pain severity was rated on a 5-point Likert scale and a 100 mm visual analogue scale. Least square mean values were generated and one-tailed t-tests were performed. RESULTS: After a single dose of ranitidine 150 mg, time to pain with oesophageal acid infusion was increased by 29% (P < 0.05) and visual analogue scale and Likert scores were decreased by 20% (P < 0.06) and 23% (P < 0.02), respectively compared with placebo. After 1 week of ranitidine, positive alterations in sensory parameters persisted. Balloon distention sensory parameters were not altered by ranitidine. CONCLUSIONS: Ranitidine significantly decreased oesophageal sensitivity to acid. Failure of ranitidine to improve balloon sensory parameters supports existence of multiple sensory pathways in the oesophagus.

Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn.

BACKGROUND: Heartburn self-treatment with antacids is extremely common. If the oesophagus is the primary site of antacid action, chewable antacids might raise the oesophageal pH more effectively than swallowable tablets. AIM: To establish a model to assess postprandial acid reflux and to compare the onset and duration of action on oesophageal pH of different antacid formulations. METHODS: Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a meal consisting of chili, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected. RESULTS: Mean intra-oesophageal pH remained lower than baseline for more than 1 h (pH range 5-5.5) postprandially, indicating reflux of somewhat acidic intragastric contents into the oesophagus. The onset of action on oesophageal pH was similar for all antacids (30-35 min). The duration of action on pH varied: chewable tablets and effervescent bicarbonate had relatively long durations of action (oesophagus, 40-45 min; stomach, 100-180 min); swallowable tablets had little effect. CONCLUSIONS: The meal model used in this study dependably produced acidic gastro-oesophageal reflux. Antacids increased oesophageal pH independent of gastric pH, demonstrating that chewing antacids controls oesophageal acidity more effectively than swallowing antacid tablets.

Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. RBC H. pylori Study Group.

AIM: To compare the efficacy of the coadministration of ranitidine bismuth citrate plus the antibiotic clarithromycin, with ranitidine bismuth citrate alone or clarithromycin alone for the healing of duodenal ulcers, eradication of H. pylori and the reduction of ulcer recurrence. METHODS: This two-phase, randomized, double-blind, placebo-controlled, multicentre study consisted of a 4-week treatment phase followed by a 24-week post-treatment observation phase. Patients with an active duodenal ulcer were treated with either ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus placebo t.d.s. for first 2 weeks; placebo b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; or placebo b.d. for 4 weeks plus placebo t.d.s. for the first 2 weeks. RESULTS: Ulcer healing rates after 4 weeks of treatment were highest with ranitidine bismuth citrate plus clarithromycin (82%) followed by ranitidine bismuth citrate alone (74%; P = 0.373), clarithromycin alone (73%; P = 0.33) and placebo (52%; P = 0.007). Ranitidine bismuth citrate plus clarithromycin provided significantly better ulcer symptom relief compared with clarithromycin alone or placebo (P < 0.05). The coadministration of ranitidine bismuth citrate plus clarithromycin resulted in significantly higher H. pylori eradication rates 4 weeks post-treatment (82%) than did treatment with either ranitidine bismuth citrate alone (0%; P < 0.001), clarithromycin alone (36%; P = 0.008) or placebo (0%; P < 0.001). Ulcer recurrence rates 24 weeks post-treatment were lower following treatment with ranitidine bismuth citrate plus clarithromycin (21%) compared with ranitidine bismuth citrate alone (86%; P < 0.001), clarithromycin alone (40%; P = 0.062) or placebo (88%; P = 0.006). All treatments were well tolerated. CONCLUSIONS: The coadministration of ranitidine bismuth citrate plus clarithromycin is a simple, well-tolerated and effective treatment for active H. pylori-associated duodenal ulcer disease. This treatment regimen effectively heals duodenal ulcers, provides effective symptom relief, eradicates H. pylori infection and reduces the rate of ulcer recurrence. The eradication of H. pylori infection in patients with recently healed duodenal ulcers is associated with a significant reduction in the rate of ulcer recurrence.

Managing heartburn at the 'base' of the GERD 'iceberg': effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids.

BACKGROUND: Many individuals with heartburn self-medicate with antacids for relief of their symptoms. AIM: To compare efficacy of effervescent ranitidine to as-needed calcium carbonate antacids in subjects who self-treat heartburn. METHODS: A total of 155 subjects with frequent antacid-responsive heartburn were randomized to receive effervescent ranitidine 150 mg tablets b.d., or as-needed calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn frequency, severity, and antacid consumption were recorded daily, and quality of life was assessed at baseline, and at weeks 6 and 12. RESULTS: Heartburn frequency and severity were significantly decreased after 1 day of ranitidine (P < 0.02). By week 6, ranitidine had significantly decreased rescue antacid consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic oesophagitis healing (

Low-dose ranitidine for the relief of heartburn.

BACKGROUND: Approximately 30% of adults in the USA suffer from heartburn or related symptoms monthly; more than 20% of these sufferers experience heartburn at least once per day. Although many rely on self-medication with antacids for the relief of their symptoms, treatments that decrease gastric volume as well as increase the pH of refluxed material should be more effective in relieving heartburn. AIM: To compare the safety and efficacy of low-dose regimens of ranitidine for the relief of heartburn. METHODS: Adults with at least a 3-month history of heartburn were eligible for this randomized, double-blind, parallel group, multicentre dose-ranging study. Following a 1-week open-label run-in phase to document baseline heartburn frequency, subjects were randomized to receive treatment with one tablet of either ranitidine 75 mg (n = 491), ranitidine 25 mg (n = 504), or placebo (n = 494), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn. RESULTS: The ranitidine 75 mg regimen was clinically (> 10 percentage points) and statistically (P < 0.05) significantly more effective than placebo for all measured efficacy end-points in relieving heartburn and reducing antacid consumption. In addition, the ranitidine 75 mg regimen was superior to placebo in providing heartburn relief within 30 min of dosing that lasted for up to 12 h. Ranitidine 25 mg was observed to be statistically superior (P < 0.05) but not clinically different from placebo, as defined a priori, in providing heartburn relief. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo. CONCLUSIONS: Ranitidine 75 mg provides prompt relief of heartburn that lasts for up to 12 h and has a safety profile comparable to that of placebo.

A double-blind, placebo-controlled study of the efficacy and safety of non-prescription ranitidine 75 mg in the prevention of meal-induced heartburn.

BACKGROUND: Ranitidine 75 mg (Zantac 75) has been shown to be effective for the treatment of pre-existing heartburn symptoms. AIM: To compare the efficacy of dosing ranitidine 75 mg or placebo 30 min prior to a proven heartburn-provoking meal in completely preventing or reducing subsequent heartburn symptoms. METHODS: A randomized, double-blind, parallel methodology was used at nine investigative centres. Following a screening visit, patients ate a standard test meal consisting of chili, chips and a soft drink on two occasions. On the first occasion, patients received single-blind placebo 30 min before the meal. This meal was used to qualify patients and to ensure the onset of a minimum level of heartburn. Patients who qualified were randomized (n = 284) to receive double-blind ranitidine 75 mg or placebo 30 min before a second test meal administered 4-14 days later at the treatment visit. Patients recorded whether heartburn was present and rated heartburn severity by completing visual analogue scales at 15-min intervals over the 4. 5 h meal evaluation periods. RESULTS: Statistically significant differences favouring ranitidine 75 mg were determined for complete prevention of heartburn (P < 0.006), heartburn severity area under the curve (P < 0.001), a clinical success end-point (P < 0.001), and all other end-points (P < 0.001). CONCLUSIONS: These data clearly demonstrate that ranitidine 75 mg is effective in completely preventing or decreasing heartburn when administered 30 min prior to a provocative meal.

Synergy between low-dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal-induced heartburn.

BACKGROUND: The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2-receptor antagonists have not been well studied. METHODS: The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the postprandial recording period. RESULTS: There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90-min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity. CONCLUSIONS: Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal-induced heartburn as well as the actions of low-dose ranitidine and antacid. For subjects with meal-induced heartburn, treatment with low-dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.

Ranitidine, 75 mg, over-the-counter dose: pharmacokinetic and pharmacodynamic effects in children with symptoms of gastro-oesophageal reflux.

BACKGROUND: The use of over-the-counter antacids has increased in children under the age of 12 years, and has been followed by an apparent increase in the use of over-the-counter histamine-2 receptor antagonists. However, the pharmacokinetic and pharmacodynamic effects of over-the-counter histamine-2 receptor antagonists in the paediatric population are largely unknown. AIM: To evaluate the pharmacokinetics and pharmacodynamics of a single dose of the over-the-counter histamine-2 receptor antagonist, ranitidine, 75 mg, in children with symptoms of gastro-oesophageal reflux disease. METHODS: Children aged between 4 and 11 years with symptoms of heartburn suspected to be due to gastro-oesophageal reflux disease were recruited at six clinical centres. Following a single dose of either oral ranitidine, 75 mg (n=19), or placebo (n=10), recording of intragastric pH and serial blood sampling were carried out for 6 h. RESULTS: The estimated pharmacokinetic parameters of ranitidine, 75 mg, were as follows: the median Cmax value of 477 ng/mL occurred within a median of 2.5 h after dosing, and the median half-life was 2.0 h. The intragastric pH began to rise approximately 30 min after dosing with ranitidine to a peak of pH; 4. The pH in the ranitidine group remained higher than that in the placebo group throughout the 6-h evaluation period. Adverse events were generally mild. CONCLUSIONS: Ranitidine, 75 mg, significantly increased the intragastric pH in children aged 4-11 years. The pharmacokinetic and pharmacodynamic profiles were similar to those in adults. Ranitidine, 75 mg, appears to be effective for the control of intragastric acidity for 5-6 h in children aged 4-11 years.

Evaluation of the teratogenicity of morphine sulfate administered via a miniature implantable pump.

A technique has been developed for the implantation of miniature infusion pumps in pregnant mice with minimal teratogenic and toxic side effects. In 7- to 10-day pregnant CF-1 mice receiving constant low doses of morphine sulfate via the infusion pump, the results, including fetal weight reduction and various skeletal and soft tissue abnormalities, were similar to those reported in previous investigations using single injections.

Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Ondansetron Study Group.

We evaluated the efficacy and safety of oral ondansetron, a selective antagonist of 5-HT3 receptors, for the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapy (> 500 mg/m2). In this trial 324 chemotherapy-naive cancer patients, mostly females with breast cancer, were randomized to receive either placebo or ondansetron 1 mg, 4 mg, or 8 mg three times per day for 3 days. There were no differences in the doses of cyclophosphamide, doxorubicin, and methotrexate between the study groups. All ondansetron dose groups were superior to the placebo control group (p < .001) for all measured efficacy parameters (complete response, number of emetic episodes, therapeutic failures, need of rescue antiemetics). No emetic episodes were reported by 9 (12%), 29 (37%), 48 (64%), and 47 (66%) of the placebo patients and the 1-mg, 4-mg, and 8-mg dose of ondansetron patients, respectively. Nausea was reduced and food intake was improved for all the ondansetron groups. A more severe emetic response was observed in patients receiving cyclophosphamide and doxorubicin combination chemotherapy. In this subgroup of patients, 66%, 38%, 25%, and 16% of the placebo group and 1-mg, 4-mg, and 8-mg ondansetron patients, respectively, required rescue antiemetics. No significant toxic effects were observed in this study. A higher incidence of headaches and gastrointestinal complaints (constipation, abdominal pain) were observed in the three ondansetron groups. In conclusion, oral ondansetron is an effective and well-tolerated antiemetic treatment in the management of cancer patients receiving ambulatory cyclophosphamide-based chemotherapy. These results support the view that serotonin and 5-HT3 receptors play an important role in cyclophosphamide-induced nausea and vomiting.

Dual and triple therapy regimens of antisecretory agents and antibiotics for the eradication of Helicobacter pylori: an overview.

BACKGROUND: Studies evaluating therapeutic regimens that combine antisecretory agents with antibiotics for the eradication of H. pylori have reported significant variations in efficacy. METHODS: We reviewed the published literature to compare H. pylori eradication rates in patients treated with either omeprazole, ranitidine bismuth citrate (RBC), or ranitidine plus metronidazole combined with either amoxicillin or clarithromycin. RESULTS: Wide variations in H. pylori eradication rates have been reported with omeprazole plus either amoxicillin (0-100%) or clarithromycin (42-88%). Eradication rates ranging from 45% to 89% and from 74% to 94% have been reported with RBC plus either amoxicillin or clarithromycin, respectively. Eradication rates ranging from 48% to 90% have been reported with ranitidine plus metronidazole and amoxicillin and one study reported an eradication rate of 95% with ranitidine plus metronidazole and clarithromycin CONCLUSIONS: Well-controlled trials with ranitidine bismuth citrate plus clarithromycin suggest that this combination may provide the most consistent and effective regimen for the eradication of H. pylori infection.

Role of non-genomic androgen signalling in suppressing proliferation of fibroblasts and fibrosarcoma cells.

The functions of androgen receptor (AR) in stromal cells are still debated in spite of the demonstrated importance of these cells in organ development and diseases. Here, we show that physiological androgen concentration (10 nM R1881 or DHT) fails to induce DNA synthesis, while it consistently stimulates cell migration in mesenchymal and transformed mesenchymal cells. Ten nanomolar R1881 triggers p27 Ser10 phosphorylation and its stabilization in NIH3T3 fibroblasts. Activation of Rac and its downstream effector DYRK 1B is responsible for p27 Ser10 phosphorylation and cell quiescence. Ten nanomolar androgen also inhibits transformation induced by oncogenic Ras in NIH3T3 fibroblasts. Overexpression of an AR mutant unable to interact with filamin A, use of a small peptide displacing AR/filamin A interaction, and filamin A knockdown indicate that the androgen-triggered AR/filamin A complex regulates the pathway leading to p27 Ser10 phosphorylation and cell cycle arrest. As the AR/filamin A complex is also responsible for migration stimulated by 10 nM androgen, our report shows that the androgen-triggered AR/filamin A complex controls, through Rac 1, the decision of cells to halt cell cycle and migration. This study reveals a new and unexpected role of androgen/AR signalling in coordinating stromal cell functions.

Teratogenic and behavioral anomalies induced by acute exposure of mice to ethanol and their possible relation to fetal brain DNA synthesis.

Physical and behavioral anomalies of fetal alcohol syndrome were studied after the i.p. administration of a single 3- or 6-g/kg dose of ethanol (25%, v/v) to gravid mice on either day 15 or day 18 of gestation. The physical effects of ethanol administered on either day 8, day 10, or day 12 of gestation (N = 6/group) were also examined and compared to the saline-administered controls. The identification of these anomalies and the effect of ethanol on the rate of fetal brain DNA synthesis were investigated. The physical anomalies were identified by standard procedures. Behavioral anomalies were measured as the inhibition of the development of various neonatal reflexes (N = 6-13/group) as compared to the saline-administered controls. The possible mechanism for these ethanol-induced abnormalities was identified by using [3H]thymidine to measure the rate of DNA synthesis (N = 6/group) in fetal mouse brains. Blood alcohol concentrations (N = 6/group) ranged from 410.2 mg/dl at 30 min to 25.8 mg/dl at 4.5 hr following the dosage of 3 g/kg of ethanol. Concentrations following the dosage of 6 g/kg of ethanol ranged from 753.7 mg/dl at 15 min to 127.1 mg/dl at 10.5 hr postinjection. Fetal and maternal weight gains were significantly inhibited compared to those of the controls. Various cranial facial, urogenital, skeletal, and cardiovascular anomalies were observed (P less than or equal to 0.05). Delays in the onset of the air and surface righting, visual placing, and negative geotaxis reflexes were observed for the ethanol-treated neonates, as compared to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonprescription doses of ranitidine are effective in the relief of episodic heartburn.

BACKGROUND: Many Americans have heartburn or related symptoms monthly and >20% experience heartburn at least once per day. Although many self-treat episodic heartburn with nonprescription antacids, newer treatments that decrease gastric volume and increase the pH of refluxed material are proving effective and popular in relieving heartburn. AIM: To evaluate the safety and efficacy of low-dose regimens of ranitidine for the relief of heartburn. METHODS: Adults with at least a 3-month history of heartburn were eligible for this randomized, double-blind, parallel group, multicenter dose-ranging study. Following a 1-week, open-label run-in phase to document baseline heartburn frequency, subjects were randomly assigned to receive treatment with one tablet of either ranitidine, 75 mg (n = 537); ranitidine, 25 mg (n = 539); or placebo (n = 544), to be taken as needed up to four times daily for 2 weeks for the relief of heartburn. RESULTS: The ranitidine 75-mg regimen was statistically (P < 0.05) and clinically (as defined a priori as > or =10% improvement) more effective than placebo in relieving episodic heartburn and in reducing antacid consumption. Ranitidine, 25 mg, was also statistically superior (P < 0.05) to placebo in providing heartburn relief. In addition, both regimens were superior to placebo in providing heartburn relief within 30 to 45 minutes of dosing. Ranitidine continued to be as effective over placebo in the treatment of the last heartburn episode as in the treatment of the first heartburn episode. Ranitidine was also equally effective over placebo in the treatment of mild, moderate, and severe episodes of heartburn. Ranitidine, 75 mg, was statistically superior to placebo for the relief of nocturnal heartburn episodes, whereas ranitidine, 25 mg, was not. All treatments were well tolerated and adverse events occurred no more frequently with the ranitidine regimens than with placebo. CONCLUSIONS: Low-dose ranitidine provides prompt and lasting relief of heartburn and has a safety profile comparable to that of placebo.

Effect of administration of ranitidine bismuth citrate with food on the suppression and eradication of Helicobacter pylori in infected volunteers.

OBJECTIVE: This study examined the effect of administration with food on the ability of ranitidine bismuth citrate to suppress and eradicate Helicobacter pylori in 41 infected volunteers. RESULTS: After a 7-day course of treatment with ranitidine bismuth citrate (400 mg b.i.d.), 90% (18/20) of subjects who received the drug with food compared with 55% (11/20) of subjects who received the drug without food tested H. pylori-negative in a 13C-urea breath test (p = 0.031). Follow-up 13C-urea breath tests performed at least 3 months after therapy showed that H. pylori was eradicated in 14% (2/14) of subjects who received ranitidine bismuth citrate with food compared with 0% (0/18) of subjects who received ranitidine bismuth citrate without food (p = 0.183). The incidence of potentially drug-related adverse events was similar regardless of whether subjects received ranitidine bismuth citrate with or without food. Headache was the most common potentially drug-related adverse event. CONCLUSIONS: These data demonstrate that administration of ranitidine bismuth citrate with food compared with without food significantly improves the suppression of H. pylori in infected volunteers.