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Biomedical subjects

R W Chapman

Publications and source records attributed to R W Chapman.

At least 181 records · Page 10Linked to original sources
PubMed1985

Effect of verapamil on ventilation and chemical control of breathing in anesthetized rats.

The calcium channel blocker, verapamil (0.1-1.0 mg/kg, i.v.) was administered to anesthetized rats to determine its effects on ventilation and on ventilatory responses to hypoxia and CO2. Verapamil produced a dose-dependent increase in tidal volume (VT) and a decrease in respiration rate (f). The bradypnea due to verapamil was characterized by an increase in expiratory duration (TE) and no change of inspiratory duration (TI). Verapamil produced similar changes in VT and f in vagotomized rats. The increase in respiration rate and minute volume due to hypoxia were inhibited by verapamil (0.5 and 1.0 mg/kg) but the increase in tidal volume due to hypoxia was depressed only with the 1.0 mg/kg dose. On the other hand, the increase in VT due to breathing CO2 was not changed by verapamil (0.1-1.0 mg/kg), but depression of the respiratory frequency response to CO2 occurred with 1.0 mg/kg of verapamil. These results indicate that verapamil produced slow, deep breathing and these responses were not mediated by vagal mechanisms. Ventilatory responses to hypoxia were depressed by verapamil. However, since the calcium blocker demonstrated no effect on the VT-CO2 relationship, verapamil did not change ventilatory chemosensitivity to CO2. The data also suggest that mechanisms governing the control of respiratory frequency are more sensitive to verapamil than tidal volume responses.

Anesthesia↗
PubMed1985

Hyperventilation-induced bronchoconstriction in guinea pigs.

The purpose of this study was to investigate the pulmonary effects of hyperventilation in anesthetized, mechanically ventilated guinea pigs. Airway resistance (Raw), dynamic lung compliance (CDyn), blood pressure (BP), heart rate (HR), arterial blood gases (PaO2, PaCO2), pH and arterial plasma HCO3- were measured before and after a 10-min period of hyperventilation produced by increasing the respiratory rate from 60 to 120 breaths/min while maintaining tidal volume at 4 ml. There was a significant increase in Raw and decrease in CDyn lasting up to 20 min after hyperventilation was stopped with no change in BP and HR. PaO2 was reduced from 109 +/- 3 mm Hg before to 53 +/- 7 mm Hg at 5 min after hyperventilation. The Raw and CDyn changes were prevented and reversed with the bronchodilators salbutamol and aminophylline indicating that reversible bronchospasms are induced in guinea pigs following a period of hyperventilation. Additional studies demonstrated that the pulmonary mechanical responses to hyperventilation were not changed by vagotomy, ventilation with high CO2 or by pretreatment with chlorpheniramine, methysergide, atropine, indomethacin, FPL 55712 or calcium-influx blockers. These results indicate that neither vagal reflexes, airway hypocapnia, receptors of histamine, serotonin, acetylcholine nor the products of arachidonic acid metabolism were involved in hyperventilation-induced bronchospasm in guinea pigs.

Airway Resistance↗
PubMed1985

Primary sclerosing cholangitis--an immunologically mediated disease?

Primary sclerosing cholangitis (PSC) is an uncommon, chronic disorder characterized by inflammatory fibrosis usually involving the entire biliary tree. The etiology has been unknown, but PSC is closely associated with ulcerative colitis, which coexists in more than two thirds of patients with PSC. In recent studies 3% to 5% of all patients with ulcerative colitis had PSC. We propose that PSC is, at least in part, an immunologically mediated disease; it is closely associated with human leckocyte antigens B8 and DR3, and circulating autoantibodies to colon and portal tract are frequently present. The anticolon antibody cross-reacts with enteric Escherichia coli. The disease may possibly be triggered in susceptible patients with ulcerative colitis by immunization with antigens shared between enteric microorganisms and the biliary system.

Autoimmune Diseases↗
PubMed1985

Comparison of the protective effect of orciprenaline with an orciprenaline-oxymetazoline combination on experimental bronchospasm in guinea pigs.

alpha-Adrenergic agonists with pulmonary vasoconstrictor activity could potentiate or prolong the bronchodilator action of a locally administered beta-adrenergic agonist by decreasing transpulmonary absorption of the compound. Results of studies using the alpha-agonist oxymetazoline and the beta-agonist orciprenaline (metaproterenol) showed that the combination of oxymetazoline [0.3 microgram] with orciprenaline (3 micrograms) offered no potency advantage and only a small duration advantage over orciprenaline alone in antagonizing a histamine-induced bronchospasm in guinea pigs. Higher doses (10 and 30 micrograms) of oxymetazoline caused bronchoconstriction when given alone and inhibited the bronchodilator action of orciprenaline. The relevance of these findings for human asthmatics hyperresponsive to the bronchoconstrictor action of alpha-agonists is discussed.

Animals↗
PubMed1984

Enkephalin heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe)-induced bronchospasm in guinea pigs: a non-naloxone reversible phenomenon.

Enkephalin heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MEAP ), is an enkephalin-related peptide derived from pre-pro-enkephalin A. Distribution studies have shown that MEAP is localized in the lung; in this organ there is very little Met-enkephalin (ME). To test the direct actions of MEAP in a tissue where it is differentially distributed from ME, MEAP was given intratracheally to anesthetized guinea pigs. MEAP produced a dose-related bronchospasm characterized by a slow onset (30-90 sec) and a duration exceeding 5 min. No significant effects on heart rate or blood pressure were observed concomitant with the pulmonary effects. ME or ethylketocyclazocine, tested at the same doses as MEAP , did not produce a bronchospasm. Moreover, naloxone failed to block MEAP 's effects. Therefore, it appears as if the MEAP -induced bronchospasm does not have an opioid-related mechanism of action. The bronchospasm produced by MEAP was not blocked by an anti-histamine (chlorpheniramine) or by vagotomy. However, inhibition of cyclo-oxygenase by ibuprofen blocked the MEAP -induced bronchospasm, suggesting that an arachidonic acid metabolite was involved in the effect. Blockade of MEAP 's pulmonary effects by an inhibitor of thromboxane synthetase (SQ 80338) and not by a leukotriene antagonist (FPL 55712) implied that MEAP 's mechanism of action may be via bronchospastic thromboxanes. These data are the first to demonstrate a non-opioid, thromboxane-mediated action of an enkephalin-related peptide.

Animals↗
PubMed1984

Effect of extra- and intracellular calcium blockers on histamine and antigen-induced bronchospasms in guinea pigs and rats.

The extracellular calcium antagonists, nifedipine and verapamil, the mixed extra/intracellular calcium antagonist diazoxide and the intracellular calcium antagonist TMB-8 were studied for their effects on histamine-induced bronchospasm in guinea pigs and on antigen-induced bronchospasms in guinea pigs and rats when administered directly to the tracheobronchial tree. Nifedipine and verapamil inhibited histamine and antigen-induced bronchoconstriction in guinea pigs, and verapamil was effective in preventing antigen-induced bronchospasms in rats. However, using doses of the extracellular blockers which produce these pulmonary effects, significant reduction of blood pressure occurred in both guinea pigs and rats. Diazoxide was inactive against histamine and antigen-induced bronchoconstrictions in guinea pigs. TMB-8 was inactive against histamine and antigen-induced bronchospasm in guinea pigs and rats. These studies demonstrate the antibronchoconstrictor activity of extracellular Ca2+ antagonists in guinea pigs and rats, but indicate that intracellular Ca2+ antagonists are not antibronchospastic agents in these species in vivo.

Albuterol↗
PubMed1983

Association of primary sclerosing cholangitis with HLA-B8.

The frequency of HLA antigens was studied in 25 patients with primary sclerosing cholangitis and compared with a control group of 562 kidney donors. Fourteen patients also had ulcerative colitis. A significant increase in the frequency of HLA-B8 (60%) was found in the primary sclerosing cholangitis patients compared with controls (25%) (p less than 0.001). HLA-B8 was found in eight patients with ulcerative colitis. The frequency of HLA-B12 was significantly decreased (8%) compared with controls (30%) (p less than 0.02). Piecemeal necrosis was observed on liver histology in 66% of HLA-B8 positive and 50% of HLA-B8 negative patients. Low titres of serum autoantibodies were frequently found in the primary sclerosing cholangitis group but did not correspond to the presence of HLA-B8. Raised serum concentrations of IgM and IgG were not related to HLA-B8. This study has shown that in patients with primary sclerosing cholangitis there exists a disease susceptibility gene closely associated with the B locus of the major histocompatibility complex which may be modified by other factors such as ulcerative colitis. Patients with ulcerative colitis and HLA-B8 may be particularly liable to develop primary sclerosing cholangitis.

Autoantibodies↗
PubMed1983

Ulcerative colitis and persistent liver dysfunction.

Six hundred and eighty-one patients with ulcerative colitis who attend the outpatient clinic in Oxford have been screened for the presence of persistently abnormal liver function tests. Of the 21 patients (3.0 per cent) found with abnormal liver function 17 (2.4 per cent) were shown by cholangiography to have primary sclerosing cholangitis. The liver biopsies from those patients demonstrated a wide range of histological features and were diagnostic of primary sclerosing cholangitis in only 50 per cent of the patients. When persistently abnormal liver function tests are demonstrated in patients with ulcerative colitis it is likely that primary sclerosing cholangitis will be present (81 per cent of patients in this study), and in order to make a reliable diagnosis it is necessary to perform cholangiography in addition to liver biopsy. A close association with primary sclerosing cholangitis and histocompatibility antigens HLA B8 and DR3 is also reported.

Adolescent↗
PubMed1982

Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis.

Liver iron concentrations were determined in 60 alcoholics with liver disease of varying severity, 15 patients with untreated idiopathic hemochromatosis, and 16 control subjects with biliary tract disease. Mean liver iron concentrations (microgram/100 mg dry weight) were significantly greater in the alcoholics (156.4 +/- 7.8 (SEM); P less than 0.05) and in patients with idiopathic hemochromatosis (2094.5 +/- 230.7; P less than 0.01) than in control subjects (53.0 +/- 7.0). Liver iron concentrations of greater than 140 micrograms/100 were found in 17 alcoholics (29%) and in all 15 patients with idiopathic hemochromatosis. Liver iron concentrations greater than 1000 micrograms/100 mg were found in all patients with idiopathic hemochromatosis but in none of the alcoholics. In the alcoholics no relationship existed between liver iron concentrations and the amount of alcohol consumed daily, the length of the drinking history, the amount of beverage iron consumed daily, or the severity of the liver disease. Serum ferritin concentrations reflected iron stores in patients with hemochromatosis and in alcoholics with minimal liver disease. However, in alcoholics with significant liver disease serum ferritin concentrations did not reflect iron stores accurately, although with normal values iron overload is unlikely. Serum iron concentration and percentage saturation of total iron-binding capacity were of little value in assessing iron status in either alcoholics or patients with hemochromatosis. Measurement of the liver iron concentration clearly differentiates between alcoholics with significant siderosis and patients with idiopathic hemochromatosis.

Alcoholism↗
PubMed1982

Binding of serum ferritin to concanavalin A in patients with iron overload and with chronic liver disease.

Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in all patients with iron overload, and with the units of blood transfused in non-chelated thalassaemic patients. The total serum ferritin showed a significant correlation with serum aminotransferase for the group of 84 patients. In the thalassaemic patients the ferritin binding to concanavalin A also correlated with aminotransferase. However, in the other groups it was the ferritin not binding to concanavalin A which showed a significant correlation with aminotransferase activity. These results suggest that measuring the fraction of serum ferritin which binds to concanavalin A does not offer any advantage over estimation of the total serum ferritin concentration in the assessment of iron stores in patients wit iron overload and liver damage.

Binding Sites↗
PubMed1982

Effect of ascorbic acid deficiency on serum ferritin concentration in patients with beta-thalassaemia major and iron overload.

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.

Adolescent↗
PubMed1982

Brain hypoxia and control of breathing: role of the vagi.

Vagally mediated reflexes play an important role in the generation of respiratory responses to various stimuli. This study examined the role of vagally mediated mechanisms in the generation of the respiratory responses to progressive brain hypoxia secondary to carboxyhemoglobinemia (HbCO 0-55%) in six unanesthetized goats. Ventilation, respiratory cycle timing, and the lung inflation reflex were measured before and during CO inhalation in intact and bilaterally vagotomized animals. Our results indicate that vagal reflexes contribute a small magnitude of the hyperpnea caused by carboxyhemoglobinemia. Furthermore, in contrast to that reported for CO2 inhalation, the tachypneic nature of the ventilatory response to CO is not a vagally mediated phenomenon. CO inhalation had a biphasic influence on the strength of the lung inflation reflex measured as the ratio of inspiratory time during occlusion (TIoccl) to inspiratory time of the preceding spontaneous breath (TIspont). At HbCO levels of 35%, TIoccl/TIspont was enhanced, whereas at HbCO levels of 55% of ratio fell to unity, indicating abolition of the reflex. After vagotomy, this ratio was unity at all levels of carboxyhemoglobinemia.

Animals↗
PubMed1982

The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis.

In patients with primary biliary cirrhosis, the chronic cholestasis, salivary, and lacrimal hyposecretion suggest that the disease is a "dry gland" syndrome. To determine whether or not pancreatic damage occurs in primary biliary cirrhosis and other forms of chronic cholestasis, we have studied pancreatic structure and function in primary biliary cirrhosis, and primary sclerosing cholangitis. In a retrospective study, retrograde pancreatograms were abnormal in 43% of 35 patients with primary biliary cirrhosis and 15% of 20 patients with primary sclerosing cholangitis (p less than 0.02). In a prospective study, serum pancreatic isoamylase was abnormal in 56% of 41 patients with primary biliary cirrhosis and 36% of 22 patients with primary sclerosing cholangitis (NS), indicating pancreatic damage in both diseases. After secretin-pancreozymin stimulation, patients with primary biliary cirrhosis, but not patients with primary sclerosing cholangitis, showed a significant reduction in duodenal juice flow rate (p less than 0.01) and immunoreactive trypsin output (p less than 0.01). The reduced trypsin output in patients with primary biliary cirrhosis indicates pancreatic hyposecretion. In neither patients with primary biliary cirrhosis nor patients with primary sclerosing cholangitis was the immunoreactive trypsin concentration, or tryptic activity in duodenal juice, significantly different from controls. Pancreatic involvement in primary biliary cirrhosis is closely associated with Sjogrens syndrome, and it is likely that the pancreatic hyposecretion is a component of the sicca complex. This association was not obvious in primary sclerosing cholangitis.

Cholangitis↗