PubMed Health⌕ Search

Biomedical subjects

A M Sawyerr

Publications and source records attributed to A M Sawyerr.

At least 19 recordsLinked to original sources
PubMed1996

Morning versus evening dosing of lansoprazole 30 mg daily on twenty-four-hour intragastric acidity in healthy subjects.

BACKGROUND: Morning dosing is usually recommended with proton pump inhibitors, but there are few data from 24-h intragastric acidity studies comparing times of dosing. METHODS: A double-blind, placebo-controlled study was performed on the seventh day of dosing to compare the effects of lansoprazole 30 mg given either in the morning or evening on 24-h intragastric acidity in 32 healthy volunteers. RESULTS: The median integrated 24-h intragastric acidity on the seventh day of morning dosing with lansoprazole 30 mg was decreased to 36% of the placebo value, compared with 42% for evening dosing. For each daytime meal-related interval, morning dosing was significantly more effective for controlling acidity, but there was no significant difference between the regimens during the night interval (23.00-08.00 h). CONCLUSIONS: These data favour morning dosing of lansoprazole 30 mg for routine use, but patients with mainly nocturnal symptoms may be best treated by evening dosing.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Serum concentrations of von Willebrand factor and soluble thrombomodulin indicate alteration of endothelial function in inflammatory bowel diseases.

Serum concentrations of immunoreactive von Willebrand factor (vWF) and soluble thrombomodulin (TM), and vWF multimer patterns were measured to assess endothelial function in patients with inflammatory intestinal diseases. In Crohn's disease and acute infective diarrhea, vWF concentrations were significantly higher than in normal controls. In all patient groups, multimeric analysis of vWF and the concentration of serum TM were not different from normal controls. The results indicate alteration of endothelial function in inflammatory intestinal disorders. They may be compatible with the presence of localized vasculitis, but indicate that systemic endothelial destruction does not occur in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1994

Serum immunoglobulin G reactive with endothelial cells in inflammatory bowel disease.

Evidence of a humoral immune response to endothelium was sought in the sera of patients with inflammatory bowel disease. In an ELISA, IgG binding to human umbilical vein endothelial cells was found in 21% of Crohn's disease sera, 10% of ulcerative colitis sera, 6% of sera from patients with acute infective diarrhea, and 8% of normal control sera. The increased prevalence in Crohn's disease sera was significant (P < 0.05). IgG-endothelial cell binding was cell specific, was not Fc-mediated, and did not mediate complement-dependent cell lysis. It was not increased by pretreatment of cells with interleukin-1 or tumor necrosis factor. Endothelial cell binding was retained by IgG F(ab')2 fragments from one of three reactive Crohn's sera, but none of three nonreactive sera. The low prevalence of this interaction, even in patients with immunohistochemically confirmed vasculitis, makes it unlikely that Crohn's disease is determined by a humoral autoimmune response to endothelium.

Adult↗
PubMed1994

Effects of ranitidine 150 mg four times a day on 24-hour intragastric acidity and 24-hour plasma gastrin concentration.

Twenty-four-hour integrated intragastric acidity and 24-hr integrated plasma gastrin concentration was measured twice in 23 healthy male volunteers on the seventh day of oral dosing with placebo or ranitidine 150 mg four times a day. The study was a randomized, double-blind, placebo-controlled, two-way crossover investigation. The mean integrated 24-hr intragastric acidity during dosing with ranitidine 150 mg four times a day decreased to 32% of the placebo value (placebo 825 mmol/hr/liter; ranitidine 265 mmol/hr/liter). The mean integrated 24-hr plasma gastrin concentration during dosing with ranitidine 150 mg four times a day was 904 pmol/hr/liter compared with placebo (410 pmol/hr/liter)--an increase of 122%. The median number of hours of pH > 3 during dosing with placebo and with ranitidine 150 mg four times a day were 5 and 11 hr, respectively. Ranitidine 150 mg four times a day caused a significant decrease of mean integrated intragastric acidity for each meal-related interval and also during the night.

Adult↗
PubMed1993

A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation.

Patients with liver disease frequently have impaired blood coagulation. The optimal method for liver biopsy in this situation is not established. To investigate this issue we randomised 117 patients with impaired blood coagulation, in whom liver biopsy was required, to receive either transjugular or plugged-percutaneous biopsy. Seventeen patients were excluded prior to biopsy and a protocol biopsy was performed in 100 patients (44 transjugular, 56 plugged-percutaneous). Liver tissue was obtained in 97 (42 transjugular, 55 plugged-percutaneous). Plugged-percutaneous liver biopsy was quicker and easier than transjugular liver biopsy and the biopsies obtained were significantly larger (12 +/- 5 mm vs. 6 +/- 4 mm; p < 0.001). However, 2 of 56 (3.5%) patients who received plugged-percutaneous biopsy had haemorrhage which required transfusion, while none of the 44 patients who received transjugular biopsy had haemorrhage (not significant). Both methods of liver biopsy were associated with a high success rate and a low incidence of complications. Plugged-percutaneous liver biopsy provides larger biopsies but may be associated with an increased risk of haemorrhage.

Biopsy↗
PubMed1993

Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity.

The study investigated the oral absorption of two antifungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens: 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and famotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria. Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti-fungal agent. When dosed with famotidine, there was a significant 52.9% decrease of the peak intraconazole concentration (P < 0.011), and a significant 51.1% decrease of the 48-h integrated serum intraconazole concentration (P = 0.005). Famotidine-induced hypochlorhydria did not affect the absorption of fluconazole.

Adult↗
PubMed1993

Effect of ranitidine bismuth citrate on postprandial plasma gastrin and pepsinogens.

Ranitidine bismuth citrate was compared with an equipotent dose of ranitidine, to determine whether the former, by an anti-Helicobacter pylori activity, would counteract the rise of gastrin resulting from ranitidine's gastric acid antisecretory activity. Twenty four men with duodenal ulcers were studied before and on the 8th day of dosing with either ranitidine bismuth citrate 800 mg twice daily or ranitidine 300 mg twice daily (double blind, randomised, parallel groups). Fasting and postprandial plasma gastrin and plasma pepsinogen I and II concentrations were measured, and a 13C-urea breath test was performed before and on the 8th day of dosing. The 13C-urea breath tests were positive in 21 patients before dosing and remained positive in nine of nine of the ranitidine dosed patients, whereas only two of 12 patients treated with ranitidine bismuth citrate remained positive. The expected rise in meal stimulated plasma gastrin with ranitidine was seen in the 12 patients who received ranitidine but, despite suppression of H pylori urease activity in 10 of 12 patients taking ranitidine bismuth citrate, there was no attenuation of the meal stimulated gastrin rise. There was no significant difference in the mean derived (4 hour) plasma pepsinogen I and II concentrations after dosing with ranitidine or ranitidine bismuth citrate.

Adult↗
PubMed1993

Early mucosal changes in Crohn's disease.

Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause of this mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage.

Capillaries↗
PubMed1993

Ranitidine has no effect on postbreakfast ethanol absorption.

The effect of ranitidine, the H2-receptor antagonist, on the systemic bioavailability of ethanol (0.3 g/kg body weight) taken orally 1 h after breakfast, was investigated in a randomized, placebo-controlled, double-blind cross-over study. Twenty normal male subjects (age, 19-26 yr) were studied on the morning of the 8th day of twice-daily dosing with either 150 mg ranitidine or placebo. Plasma ethanol concentration was measured by the alcohol dehydrogenase method from 0 to 240 min after oral ingestion of ethanol (100% ethanol made up to 200 ml orange juice). Compared with placebo, dosing with ranitidine resulted in nonsignificant changes in either the mean integrated 4-h plasma ethanol concentration (27.8 vs. 32.4 mg.h/dl), the peak plasma ethanol concentration (18.0 vs. 21.1 mg/dl), or the time to peak (43 vs. 40 min). There is no clinically important interaction between ranitidine and a low dose of ethanol taken orally 1 h after breakfast.

Administration, Oral↗
PubMed1992

Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn's disease using the nested polymerase chain reaction.

The prevalence of herpesvirus DNA was examined in inflammatory bowel disease tissue. DNA was extracted from resection and biopsy specimens of the large intestine from patients with ulcerative colitis (n = 21), patients with Crohn's disease (n = 29), and patients with noninflammatory bowel disease (controls) (n = 21). The nested polymerase chain reaction was used to detect viral DNA using primer pairs specific for either cytomegalovirus (CMV), herpes simplex virus 1 (HSV1), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), or Epstein Barr virus (EBV). HSV1 and VZV DNA were not detected in any of tissue samples. There was a high prevalence of CMV (81%), HHV6 (76%), and EBV (76%) DNA in ulcerative colitis tissue compared to Crohn's disease tissues (CMV 66%, HHV6 45%, EBV 55%). Control tissue had a relatively low frequency of CMV (29%) and EBV (19%) DNA but a prevalence of HHV6 DNA similar to that of ulcerative colitis (86%). However, the simultaneous presence of HHV6 and CMV and/or EBV DNA in ulcerative colitis tissue (76%) was much greater than in either Crohn's disease tissues (38%) or control tissue (29%) (P < 0.05). There was a low prevalence of CMV, HHV6, and EBV DNA in peripheral blood mononuclear cells from all patient groups. CMV and EBV are capable of reactivating HHV6: the high prevalence of coexistent HHV6 infection with either or both of these two viruses in ulcerative colitis tissue suggests that they may play a synergistic role in the pathogenesis of this disease.

Adolescent↗
PubMed1992

A ferret model of acute multifocal gastrointestinal infarction.

Based on the demonstration of mural granulomatous vasculitis in Crohn's disease, it was hypothesized that this vasculitis may account for the discontinuous pattern of lesions in this condition. Accordingly, the present study investigated the histological changes produced by interruption of the submucosal and mucosal microcirculation in the ferret midgut. Two techniques were used. First, up to 30 adjacent vasa recta were ligated using microsurgical techniques; this produced no evidence of ischemic damage. Second, interruption of the submucosal collateral plexus by the intra-arterial injection of styrene microspheres (27-, 50-, or 90-microns diameter) produced acute intestinal mucosal damage. A combination of 27- and 90-microns spheres resulted in focal mucosal inflammation, necrosis, and ulceration. "Summit" lesions with normal adjacent mucosa were observed 48 hours after embolization, with evidence of regeneration of the mucosa overlying the occluded vessels at 72 hours. This model shows that focal gastrointestinal infarction with normal adjacent mucosa can be produced by acute occlusion of submucosal and mucosal arteries.

Acute Disease↗
PubMed1992

Evidence for activation of coagulation in Crohn's disease.

Haemostatic changes in 16 patients with Crohn's disease were studied from active disease into clinical remission and beyond. Elevated concentrations of fibrinopeptide A (FpA) and prothrombin fragments F1 + 2 (F1 + 2) were found at times of both active (FpA median 3.2, range [0.3-40] ng/ml and F1 + 2 median 2.3, range [0.3-18] nm/l) and inactive disease (FpA median 2, range [0.4-40] ng/ml and F1 + 2 median 1.3, range [0.2-20) nm/l]. We also measured the physiological inhibitors of coagulation and fibrinolysis; there was no significant difference in the levels of antithrombin III, protein C or the Exner ratio between active and inactive disease. Free protein S levels were significantly lower in active disease (median 34, range 9-54 U/dl) than in remission (median 40, range 12-65 U/dl). Plasminogen activator inhibitor type 1 (PAI-1) was significantly raised in remission (median 11, range 3-32 ng/ml) when compared to active disease (median 7, range 3-42 ng/ml). The D-dimer correlated significantly with fibrinopeptide A (P < 0.001), suggesting reactive fibrinolysis in some patients. Most (35/52, 67%) samples showed evidence of persistent haemostatic activation (elevated FpA and/or F1 + 2) during phases of apparent clinical remission in Crohn's disease, a factor that is not reflected by clinical activity scores. This study supports the hypothesis that coagulation is activated in the mesenteric vasculature of patients with Crohn's disease.

Adolescent↗
PubMed1992

Short report: the effect of ranitidine on the post-prandial absorption of a low dose of alcohol.

Twenty healthy male subjects were studied twice using a double-blind, randomized placebo controlled, cross-over study design. Alcohol absorption (integrated 2-h plasma alcohol concentration, peak plasma alcohol concentration, and time to reach peak concentration) was measured after 8 daily doses of either placebo or 300 mg ranitidine. They were given alcohol, 0.15 g/kg of body weight by month after an evening meal. Compared with placebo, there was a trend towards higher integrated 2-h plasma alcohol concentrations (3.17 and 3.89 mg. h/dL, respectively, P = 0.07), and a statistically significant increase in mean peak plasma alcohol concentration after dosing with ranitidine (4.92 and 6.47 mg/dL, respectively, P = 0.05).

Adult↗
PubMed1992

Ranitidine, cimetidine, famotidine have no effect on post-prandial absorption of ethanol 0.8 g/kg taken after an evening meal.

Forty-seven healthy male subjects were studied twice using a randomized, placebo-controlled design. Each subject took an 8-day course of two of the following four regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic bioavailability of ethanol (integrated 6-h plasma ethanol concentration, peak plasma ethanol concentration, and the time to peak plasma ethanol concentration) was measured after the oral ingestion of 0.8 g of ethanol per kg body weight, given one hour after an evening meal on Day 8 of each regimen. There was no significant difference of integrated 6-h plasma ethanol concentration, peak ethanol concentration, or time to reach peak ethanol concentration after dosing with either ranitidine, cimetidine or famotidine or placebo.

Absorption↗
PubMed1991

Smoking, the oral contraceptive pill, and Crohn's disease.

Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease.

Blood Coagulation↗
PubMed1991

Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole.

The magnitude and duration of changes in nocturnal intragastric acidity caused by 25 days of dosing with the antisecretory drugs ranitidine and omeprazole were investigated in a double-blind study of 22 healthy subjects. Nocturnal intragastric acidity was studied before (twice), during (on day 25), and after (every 3 days for 21 days) dosing with either 300 mg ranitidine at night or 40 mg omeprazole every morning. Three and six days after withdrawal of dosing with ranitidine, median integrated nocturnal intragastric acidity was increased significantly (17% and 14%, P = 0.01 and P = 0.05, respectively) compared with before dosing. Three days after withdrawal of dosing with omeprazole, median integrated nocturnal intragastric acidity was decreased significantly (-23%, P = 0.003). Compared with before dosing, no significant differences were seen in the ranitidine group between days 9 and 21 or the omeprazole group between days 6 and 21 after cessation of dosing. Fasting plasma gastrin concentration was measured on the morning of each study; compared with before treatment, the only significant elevations occurred on the last day of dosing with omeprazole (before, 4 pmol/L; during, 7 pmol/L). It is concluded that rebound intragastric hyperacidity after dosing with 300 mg ranitidine at night or sustained hypoacidity after dosing with 40 mg omeprazole every morning reflect transient disturbances of gastric function that are unlikely to be of clinical importance.

Adult↗
PubMed1991

The effect of histamine H2-receptor blockade on bismuth absorption from three ulcer-healing compounds.

Twelve healthy male subjects were dosed with six regimens: ranitidine and De-Noltab (tripotassium dicitrato bismuthate; Gist-Brocades Ltd., Weybridge, England), placebo and De-Noltab, ranitidine and Pepto-Bismol liquid [bismuth salicylate; Procter & Gamble (Health and Beauty Care) Ltd., Egham, England], placebo and Pepto-Bismol, ranitidine and Roter tablets (bismuth subnitrate; Roter Pharma Ltd., Ashford, England), and placebo and Roter. Ranitidine, 300 mg, or placebo was administered at 10 PM (night before) and at 7 AM; at 9 AM, the oral dose of bismuth was either 2 De-Noltabs, 3 30-mL doses of Pepto-Bismol liquid, or 2 Roter tablets. When predosed with placebo, the median integrated 8-hour plasma bismuth concentration was significantly greater after dosing with De-Noltabs than after dosing with either Pepto-Bismol or Roter (61, 8, and 8 ng.h/mL, respectively), with a similar trend for 8-hour median urinary bismuth excretion (213, 40, and 6 micrograms, respectively). When predosed with ranitidine, only after De-Noltab administration were there significant increases in the 8-hour plasma bismuth concentration (147 ng.h/mL), and 8-hour urinary bismuth excretion (686 micrograms). Eliminating intragastric acidity may enhance bismuth absorption after oral dosing with De-Noltabs by maintaining intragastric tripotassium dicitrato bismuthate as a colloidal suspension.

Adult↗