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Biomedical subjects

R W Chapman

Publications and source records attributed to R W Chapman.

At least 19 recordsLinked to original sources
PubMed1992

Misuse of ecstasy.

Explore the source record for details and available documents.

3,4-Methylenedioxyamphetamine↗
PubMed1992

(R)-alpha-methylhistamine augments neural, cholinergic bronchospasm in guinea pigs by histamine H1 receptor activation.

In the airways, activation of histamine H3-receptors with (R)-alpha-methylhistamine inhibits neurally induced cholinergic contractions in vitro and peptidergic responses in vivo. The role of histamine H3-receptors on the cholinergic bronchoconstriction induced by electrical stimulation of the dorsal medulla in guinea pigs was assessed in this study. There was no evidence for an H3-receptor mediated inhibition of cholinergic bronchospasm in vivo. However, there was potentiation of central cholinergic bronchoconstriction by (R)-alpha-methylhistamine or histamine by a mechanism involving H1-receptors. I.v. (R)-alpha-methylhistamine (0.3-3 mg/kg) or histamine (0.001-0.01 mg/kg) produced a transient bronchospasm and potentiated the bronchoconstriction due to medullary stimulation. These effects of (R)-alpha-methylhistamine and histamine were blocked by the histamine H1-antagonist, chlorpheniramine (30 micrograms/kg i.v.) but not by H2- or H3-receptor antagonists. (R)-alpha-Methyl-histamine did not potentiate the bronchoconstriction due to i.v. methacholine. Other bronchoconstrictor agents such as methacholine and serotonin did not potentiate the CNS-induced bronchospasm.

Animals↗
PubMed1992

Primary sclerosing cholangitis: refinement and validation of survival models.

The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation.

Adult↗
PubMed1992

A survey of cytomegalovirus (CMV) DNA in primary sclerosing cholangitis (PSC) liver tissues using a sensitive polymerase chain reaction (PCR) based assay.

Reactivation of cytomegalovirus (CMV) has been implicated as a possible etiological agent in primary sclerosing cholangitis (PSC) partly because of the ability of CMV infection to cause hepatobiliary damage, and further because of the recent recognition of a PSC-like syndrome in AIDS patients, many of whom have hepatobiliary infection with CMV. Direct evidence of CMV infection in PSC has come from a study detecting CMV DNA in 7/7 PSC livers, but only 5/20 controls. We have developed an assay for CMV-DNA by amplification of the immediate early region of CMV using the polymerase chain reaction, followed by Southern blotting and 32P oligoprobing of the amplification product. This system has an average sensitivity of at least 25 copies of CMV-DNA per 5000 formalin-fixed paraffin-embedded cells. 37 PSC and 19 control samples of formalin-fixed paraffin-embedded hepatobiliary tissues were studied. Amplification for the beta-globin in each sample was used as an amplification control, and fetal lung with known CMV infection as the CMV-positive control. 37/37 PSC tissues amplified for beta-globin, and one of these was positive for CMV-DNA. All 19 controls amplified for beta-globin, with none being positive for CMV. The lack of CMV-DNA in 35/36 PSC samples at a level of 25 copies per 5000 cells, we believe, rules out any significant CMV reactivation in these tissues, and suggests that CMV replication and re-activation is not responsible for the progression of PSC.

Base Sequence↗
PubMed1992

Inhibition of sympathetic hypertensive responses in the guinea-pig by prejunctional histamine H3-receptors.

1. The effect of (R)-alpha-methylhistamine, a selective H3-histamine receptor agonist, was examined on the neurogenic hypertension and tachycardia that is induced by stimulation of areas in the medulla oblongata of guinea-pigs. Electrical medullary stimulation (32 Hz, 3-5 s trains, 0.5-1.0 ms square pulse, 25-400 microA) produced intensity-dependent increases in blood pressure and a more variable tachycardia. 2. (R)-alpha-methylhistamine inhibited the hypertension and tachycardia due to submaximal CNS stimulation. The inhibition of hypertension by (R)-alpha-methylhistamine was dose-dependent (10-300 micrograms kg-1, i.v.) and was not seen at high intensities of stimulation. 3. (R)-alpha-methylhistamine (300 micrograms kg-1, i.v.) did not attenuate the pressor response to adrenaline (1 and 3 micrograms kg-1, i.v.), indicating that the effect of (R)-alpha-methylhistamine was not mediated by a postjunctional action on smooth muscle. 4. The inhibition of CNS-induced hypertension by (R)-alpha-methylhistamine (300 micrograms kg-1, i.v.) was blocked by the H3 antagonists, thioperamide (ID50 = 0.39 mg kg-1, i.v.), impromidine (ID50 = 0.22 mg kg-1, i.v.) and burimamide (ID50 = 6 mg kg-1, i.v.). The rank order potency of these antagonists is consistent with activity at the H3B receptor subtype. Chlorpheniramine (30 micrograms kg-1, i.v.) and cimetidine (3 mg kg-1, i.v.) did not antagonize the inhibition of CNS-hypertension by (R)-alpha-methylhistamine. 5. These results suggest that (R)-alpha-methylhistamine inhibits sympathetic hypertensive responses in guinea-pigs by activation of prejunctional H3-receptors, possibly located on postganglionic nerve terminals. Furthermore, on the basis of the rank order potency to different H3-antagonists, it appears that the H3B-receptor subtype is involved with H3-receptor responses on vascular sympathetic nerves.

Animals↗
PubMed1992

Prevalence of anti-neutrophil antibody in primary sclerosing cholangitis and ulcerative colitis using an alkaline phosphatase technique.

The detection of a nuclear anti-neutrophil antibody in patients with primary sclerosing cholangitis (PSC), using an immunoperoxidase technique, was recently reported by us. Subsequently, detection of a cytoplasmic anti-neutrophil antibody was reported by others, using a two stage procedure of enzyme linked immunosorbent assay followed by an immunofluorescent method. Detection of cytoplasmic anti-neutrophil antibody in PSC, which, in contrast to that two stage procedure, uses a simple one step immuno-alkaline phosphatase method is now reported. Normal human neutrophils were cytocentrifuged, ethanol fixed, and then incubated with coded patients' sera. Rabbit anti-human immunoglobulin conjugated with alkaline phosphatase was used to detect the bound antibody. Fast red was used to visualise the reaction. Twenty three of 30 (77%) PSC patients showed positive granular cytoplasmic staining (with some perinuclear accentuation) with a network of cytoplasmic filaments. Fifteen of 45 (33%) ulcerative colitis patients and 1 of 3 chronic active hepatitis patients showed similar staining. Thirty five of 152 patients with ulcerative colitis, chronic active hepatitis, and a variety of other liver diseases showed a different pattern of cytoplasmic labelling, with no surrounding filaments. Seventy nine patients, including seven PSC patients and 33 normal subjects, were negative. In comparison, 86% of PSC patients, 57% of patients with primary biliary cirrhosis, 50% of normal subjects, and well over 60% of patients with ulcerative colitis, Crohn's disease, alcoholic liver disease, and chronic active hepatitis were positive using the one step immunofluorescent method. This method is more specific for PSC than those described in recent reports and may be of diagnostic importance.

Adult↗
PubMed1991

Ruthenium red decreases capsaicin and citric acid-induced cough in guinea pigs.

The influence of aerosols of Ruthenium red (RR) on capsaicin- and citric acid-induced cough was investigated in guinea pigs. Aerosols of RR (0.3, 1, 3%) reduced capsaicin-induced cough in dose-dependent manner. Inhalation of RR also reduced cough produced by low, (200 mM) but not high (550 mM), concentrations of citric acid. These data suggest that RR is not a specific capsaicin antagonist and that citric acid and capsaicin share a common mechanism for activation of airway C-fibers that is RR sensitive. Furthermore, high concentrations of citric acid can elicit cough through a RR-insensitive mechanism.

Aerosols↗
PubMed1991

Carcinoma of the gallbladder in ulcerative colitis and primary sclerosing cholangitis. Report of two cases.

The authors present the cases of two patients with carcinoma of the gallbladder complicating chronic ulcerative colitis. Both patients had concomitant primary sclerosing cholangitis. Twelve such cases of gallbladder carcinoma have been reported in the literature. The presence of primary sclerosing cholangitis in patients with ulcerative colitis is associated with malignancy of the extrahepatic biliary tree. It is suggested that, if colectomy is necessary, the liver should be biopsied and a cholecystectomy performed if the gallbladder is deemed abnormal.

Aged↗
PubMed1991

Prejunctional GABA-B inhibition of cholinergic, neurally-mediated airway contractions in guinea-pigs.

GABA is a known inhibitory neurotransmitter in the CNS. Recent studies have also demonstrated the presence of GABA in peripheral tissue, including lung. To delineate a role for GABA in lung, the effect of GABA and selective GABA agonists and antagonists on neuronally-induced airway contractions in guinea pigs were studied. In vitro, tracheal contractions induced by electrical field stimulation (EFS) were inhibited by tetrodotoxin and atropine indicating that the contractions were mediated by neuronal release of acetylcholine. The contractions caused by EFS, but not those by exogenous acetylcholine, were inhibited by GABA (EC50 = 4.5 microM) and the selective GABA-B agonist baclofen (EC50 = 9 microM), but not by the GABA-A agonist, muscimol. The inhibitory effect of baclofen was not affected by the GABA-A antagonist, bicuculline, but was significantly reversed with the GABA-B antagonists, 3-aminopropylphosphonic acid (3-APPA) (pA2 = 4.5) and 2-hydroxysaclofen (pA2 = 4.1). In vivo, vagal nerve stimulation (5 V, 20 Hz, 0.5 ms, 5 s) in anesthetized, mechanically ventilated guinea-pigs caused cholinergic-dependent bronchospasms that were inhibited by intravenous GABA (3 and 10 mg/kg) and baclofen (1-10 mg/kg), but not by muscimol. The inhibitory effects of GABA and baclofen against vagal bronchospasm were blocked by 3-APPA (5 mg/kg, i.v.), but not by bicuculline. Responses to the GABA-B agonists were unaltered after the treatment of animals with phentolamine or propranolol to block alpha-adrenergic and beta-adrenergic receptors, respectively. Bronchospasm due to intravenous methacholine was also unchanged by GABA and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Sch 37370: a new drug combining antagonism of platelet-activating factor (PAF) with antagonism of histamine.

Multiple mediators are involved in the pathophysiology of allergic and inflammatory disorders. Drugs that affect the action of more than one mediator may, therefore, be particularly effective in these disorders. Two such mediators are platelet-activating factor (PAF) and histamine. From a structural series with documented antihistamine activity, Sch 37370 has been identified as a dual antagonist of PAF and histamine. In vitro, Sch 37370 selectively inhibits PAF-induced aggregation of human platelets (IC50 = 0.6 microM) and also competes with PAF binding to specific sites in membrane preparations from human lungs (IC50 = 1.2 microM). Sch 37370 also blocks the binding of [3H]pyrilamine to histamine H1 receptors in rat brain membranes. In guinea pigs, orally administered Sch 37370 is effective against bronchospasm to histamine (ED50 = 2.4 mg/kg), PAF (ED50 = 6.0 mg/kg) or serotonin (ED50 = 9.6 mg/kg). In contrast, it only weakly antagonizes methacholine-induced bronchospasm (ED50 = 51 mg/kg) and is totally inactive at 50 mg/kg against bronchospasm due to leukotriene C4 or substance P. Sch 37370 blocks hypotension in rats and a cutaneous reaction in monkeys induced by either PAF or histamine, as well as PAF-induced edema in the rat pleural cavity. In addition, Sch 37370 blocks bronchospasm induced by either antigen in sensitized guinea pigs or hyperventilation in nonsensitized guinea pigs. Sch 37370 also inhibits antigen-induced lung eosinophilia in sensitized guinea pigs and a reverse passive Arthus reaction in rats. Although Sch 37370 is not the most potent PAF antagonist or antihistamine, it is the first compound that combines these pharmacologically relevant activities and may offer important advantages over currently available antihistamine therapies.

Animals↗
PubMed1990

Selective inhibition of peripheral histamine responses by loratadine and terfenadine.

To determine the selectivity of the non-sedating antihistamines loratadine and terfenadine and the sedating antihistamine diphenhydramine for peripheral and central histamine H1-receptors, these compounds were examined against intravenous (i.v.) and intracerebroventricular (i.c.v.) histamine-induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs. Animals were prepared with i.c.v. or i.v. cannulas and instrumented for the measurement of airway resistance (RAW) and dynamic lung compliance (CDyN). Loratadine, terfenadine or diphenhydramine were administered orally 2 h before either i.v. or i.c.v. injection of histamine. Each antihistamine blocked the i.v. histamine bronchospasm with the order of potency loratadine (ED40 = 0.08 mg/kg) greater than terfenadine (ED40 = 0.44 mg/kg) greater than diphenhydramine (ED40 = 5 mg/kg). These drugs also blocked i.c.v. histamine-induced bronchoconstrictions, but loratadine and terfenadine were approximately 10 times less potent against i.c.v. histamine bronchoconstriction than they were against i.v. histamine. In contrast, diphenhydramine was equipotent against i.c.v. and i.v. histamine bronchoconstriction. These results demonstrate that the non-sedating antihistamines loratadine and terfenadine, unlike diphenhydramine, are more effective against peripheral than central H1-receptors, probably because of poor penetration of the blood-brain barrier.

Animals↗
PubMed1990

Liver transplantation for acute hepatic failure?

In the absence of definitive medical treatment for severe fulminant hepatic failure, liver transplantation may be appropriate in selected patients. However, uniform and easily applicable criteria for diagnosis of severity and analysis of results are needed to prevent unnecessary transplantation and to ensure that patients who may benefit are appropriately treated. Previous regimens for treatment of fulminant hepatic failure were often advocated, on the basis of data from historical controls, for several years until controlled trials failed to show any benefit. To obtain reliable information more rapidly than achieved before, a controlled trial between specialist liver transplant units is needed to establish the role of emergency hepatic transplantation in patients with fulminant hepatic failure.

Acute Disease↗
PubMed1990

Endoscopic sphincterotomy for the palliation of ampullary carcinoma.

Palliative endoscopic sphincterotomy was performed on 17 patients with adenocarcinoma of the ampulla of Vater. An endoprosthesis was inserted immediately after the sphincterotomy in four of the patients. Fourteen patients made uncomplicated recoveries from the procedure and their jaundice resolved completely. Early complications developed in three patients. One patient died from haemorrhage. Two patients, both of whom had an endoprosthesis, developed cholangitis. The endoprosthesis was removed and another inserted in one patient and the other underwent surgery. Both thereafter made uncomplicated recoveries. Jaundice subsequently recurred in eight patients and further endoscopic treatment was successful in five of these patients. Eleven patients died between 4 days and 23 months after the sphincterotomy with a median survival of 12 months. Four patients remain alive between 3 and 17 months after treatment. The results indicate that reasonable palliation can be achieved safely by endoscopic sphincterotomy.

Adenocarcinoma↗