Search PubMed⌕ Search

Biomedical subjects

R G Watson

Publications and source records attributed to R G Watson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of erythrocyte binding on elimination of harmol by the isolated perfused rat liver.

The effect on the hepatic elimination rate of drug bound to erythrocytes and to albumin was compared with harmol, a relatively hydrophilic drug of high hepatic intrinsic clearance, in the single-pass isolated perfused rat liver preparation (n = 12). The steady-state hepatic extraction ratio (E) of harmol (50 microM) was measured during three consecutive 35-min periods with three different perfusates: Krebs-Henseleit buffer, buffer containing bovine serum albumin (2%), and buffer containing washed human erythrocytes (10%) perfused at 5 mL/min/g liver in randomized order. The mean unbound fraction (fu) of harmol in the latter two perfusates was 0.55 +/- 0.07 and 0.62 +/- 0.08, respectively, and the mean E for the three perfusates were 0.85 +/- 0.06, 0.62 +/- 0.07, and 0.71 +/- 0.08, respectively. The sinusoidal model fitted the relationship between E and fu better than the venous equilibrium model. Four further experiments, with perfusates of buffer, buffer + 2% albumin, and buffer + 4% albumin, confirmed that harmol elimination conformed to the sinusoidal model. For each of the 12 experiments that used erythrocyte perfusate, E and fu data from each of the two non-erythrocyte perfusates were used to predict E for the erythrocyte perfusate at the observed fu of 0.62, with the sinusoidal model. There was no significant difference between the observed (0.71 +/- 0.08) and predicted (0.68 +/- 0.10) E values (p > 0.05). This result suggests that release of harmol from erythrocytes is not a rate-limiting factor in the hepatic elimination of harmol, and that plasma membrane permeability does not contribute readily to a red cell carriage effect, at least with moderately polar and small molecules.

Animals↗
PubMed1996

Effervescent and standard formulations of ranitidine--a comparison of their pharmacokinetics and pharmacology.

BACKGROUND: An effervescent formulation of ranitidine may be absorbed faster and achieve a faster onset of action than conventional tablet form. The aim of this study was to compare the effects of effervescent formulations of ranitidine with equivalent dose standard tablets, in terms of intragastric pH and plasma pharmacokinetics in the initial 6 h following dosing. METHODS: Fifteen fasting healthy males, aged 18-31 (mean 29) years, were each randomly given, at weekly intervals, 150 mg standard and effervescent ranitidine and 300 mg standard and effervescent ranitidine. Ambulatory gastric pH was performed and plasma drug levels measured at regular intervals. RESULTS: Plasma ranitidine levels increased more rapidly with both effervescent formulations compared with standard tablets as indicated by mean area under curve (AUC) at 1 h (P < 0.001). However, the pH profiles produced by all four treatments were similar with a steep rise in pH at 40-60 min to give a sustained level of pH 7 for the following 5 h. The effervescent formulations produced a transient rise in pH immediately following dosing, and for 300 mg this rise was significantly different at 10-20 min compared with the standard tablet (median pH 4.75 vs. 2.3, P < 0.05). CONCLUSIONS: Plasma drug levels increase more rapidly following effervescent ranitidine. Effervescent and standard formulations of 150 and 300 mg are all equally effective in producing gastric pH 7 after 1 h. However, effervescent formulations produce an early transient rise in pH which may be of clinical benefit.

Adolescent↗
PubMed1996

Preliminary results from follow-up of a large-scale population survey of antibodies to gliadin, reticulin and endomysium.

UNLABELLED: Coeliac disease is often under-diagnosed, particularly in cases which are atypical or asymptomatic. OBJECTIVE: The aim of this study was to comprehensively assess the prevalence and clinical profile of adult coeliac disease in our community. METHODS: One-hundred-and-thirteen subjects from the most recent MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease)1991/2 survey with positive serology were followed up 3 years after initial screening and assessed by means of (i) a clinical questionnaire, (ii) screening blood tests, and (iii) jejunal biopsy. RESULTS: Forty-six subjects (21 male, mean age 51 years) have been followed up to date. Prior to follow-up, two of these subjects were diagnosed as having coeliac disease. Ten (3 male, mean age 51 years) of 44 subjects had enteropathy. Three of these 10 subjects were relatively asymptomatic, 3 had folate deficiency and 3 had iron deficiency. Thus 12 of the 1823 initially screened had enteropathy consistent with coeliac disease. CONCLUSIONS: Coeliac disease is more prevalent than previous estimations and was found to be at least 1 in 152.

Adult↗
PubMed1996

Randomised controlled trial of ranitidine versus omeprazole in combination with antibiotics for eradication of Helicobacter pylori.

This study compared high dose ranitidine versus low dose omeprazole with antibiotics for the eradication of H pylori. 80 patients (mean age 48 years, range 18-75) who had H pylori infection were randomised in an investigator-blind manner to either a two-week regime of omeprazole 20 mg daily, amoxycillin 500 mg tid and metronidazole 400 mg tid (OAM), or ranitidine 600 mg bd, amoxycillin 500 mg tid and metronidazole 400 mg tid (RAM), or omeprazole 20 mg daily and clarithromycin 500 mg tid (OC), or omeprazole 20 mg daily and placebo (OP). H pylori was eradicated in 6 of 19 patients in the OAM group (32%); 8 of 18 in the RAM group (44%), 4 of 15 in the OC group (27%); none of 18 in the OP group (0%). [< P0.005 for OAM, RAM, OC vs OP; P = N.S. between OAM, RAM, OC]. Overall metronidazole resistance was unexpectedly high at 58%. Eradication rates in metronidazole sensitive patients were 71% (5/7) and 100% (3/3) for OAM and RAM respectively. In conclusion, H pylori eradication rates using high dose ranitidine plus amoxycillin and metronidazole may be similar to that of low dose omeprazole in combination with the same antibiotics for omeprazole with clarithromycin. Overall eradication rates were low due to a high incidence of metronidazole resistance but were higher in metronidazole-sensitive patients. Even high dose ranitidine with two antibiotics achieves a relatively low eradication rate. These metronidazole-based regimens cannot be recommended in areas with a high incidence of metronidazole resistance.

Adolescent↗
PubMed1995

Patient knowledge and prescription of ulcer healing drugs in medical inpatients.

If patients on ulcer healing drugs are ill-informed about their medication or diagnosis their lack of knowledge may prejudice them from receiving potentially beneficial treatment, such as thrombolytic therapy, because of concern about upper gastrointestinal side effects. Furthermore because ulcer healing drugs are safe and effective there is a tendency to prescribe these drugs inappropriately. We therefore assessed patients' knowledge about their ulcer healing drugs and whether the prescriptions were appropriate or not. Consecutive patients on ulcer healing drugs admitted as emergencies to the general medical take-in underwent a structured interview designed to assess knowledge of drugs prescribed prior to admission. Patient responses (fully correct, partially correct or incorrect) and appropriateness (appropriate, possibly appropriate or inappropriate) of the prescriptions were graded by reference to information obtained from hospital notes and/or general practitioner. Seventy-nine out of a total of 537 patients (15%) were on ulcer healing drugs. Mean age was 64 years (range 26-91). Fifty-five (70%) of these patients could be analysed for correctness and 62 (78%) for the appropriateness. Patients gave an incorrect indication for 18% of ulcer healing drugs but only for 10% of non-ulcer healing drugs (P < 0.05). Factors associated with a poorer knowledge of drugs overall, were increasing age and impaired mental test score but not the number of drugs the patient was taking. The trends were similar for ulcer healing drugs alone. Sixteen out of 62 (26%, 95% CI 16-39%) prescriptions for ulcer healing drugs were deemed inappropriate. Our findings demonstrate a need for greater attention to patient education about drugs, especially ulcer healing drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Low prevalence of primary biliary cirrhosis in Victoria, Australia. Melbourne Liver Group.

A prevalence study of primary biliary cirrhosis was carried out in the state of Victoria, Australia, by means of a mail survey of specialist physicians and a review of hospital records. Eighty four cases were identified, giving a prevalence of 19.1 per million population (95% confidence limits (CI) 15.3, 23.7), which is among the lowest in published reports. The prevalence in the Australian born, at risk population (women over the age of 24) was 51 per million (95% CI 37.5, 67.9). Both these figures are considerably lower than those in populations of similar age distribution in the UK and northern Europe. Since most Victorians are descended from British or European settlers, the low prevalence of primary biliary cirrhosis in this study supports the hypothesis that local environmental factors may be important in the pathogenesis of this disease.

Adult↗
PubMed1995

Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them?

We prospectively measured serum alkaline phosphatase (ALP), aspartate and alanine transaminase (AST/ALT), and tested sera for antinuclear, smooth-muscle, and antimitochondrial antibodies (ANA, SMA, AMA) in our patients with celiac sprue to determine the prevalence of associated liver abnormalities and its relevance to clinical management. Of 129 patients, ALP was the only elevated enzyme in 12 (9%) and in most cases was not thought to reflect significant liver disease. Seventeen (13%) had elevated AST and/or ALT with normal ALP. Levels normalized in 15 patients after dietary gluten exclusion and remained elevated in 2 noncompliers. Two patients (2%) with elevated AST, ALT, and ALP underwent further investigation: one had negative autoantibodies, liver biopsy, and endoscopic retrograde cholangiography and the other had ANA-positive chronic active hepatitis; enzymes in both cases improved with a gluten-free diet. There was no significant association between elevated AST/ALT and positive ANA/SMA; no patient had AMA. Abnormalities in liver enzymes are common in celiac sprue, but usually respond to dietary gluten exclusion. We propose that there is no need for invasive liver investigation in these patients unless there is more specific evidence of primary liver disease or failure of dietary response.

Adolescent↗
PubMed1994

Immune function in patients undergoing open vs laparoscopic cholecystectomy.

BACKGROUND: Abnormal release of inflammatory mediators following surgical injury is associated with immunological alteration, which may predispose to sepsis. Laparoscopic surgery is associated with reduced postoperative complications, but mechanisms are unclear. We hypothesized that early recovery following laparoscopic surgery may relate to minimal impairment of immune function. DESIGN: Analysis of the temporal immune responses in two similar groups of patients randomized to open (n = 22) vs laparoscopic (n = 22) cholecystectomy. Patients were matched for age, height, weight, and operation time. Immune parameters, including monocyte superoxide anion (O2-) and tumor necrosis factor release, neutrophil O2- levels and chemotaxis, total white blood cell counts, partial arterial oxygen pressure, and serum cortisol and C-reactive protein levels were assessed preoperatively and on postoperative days 1 and 3. RESULTS: There were significant increases (P < .001) in monocyte release of O2- and tumor necrosis factor, neutrophil release of O2- and chemotaxis, and white blood cell count in the open vs laparoscopic cholecystectomy study groups, with a concommitant decrease in partial arterial oxygen pressure. These findings correlated with significantly higher postoperative septic complications in the open cholecystectomy group (P < .05). There were no significant differences in either plasma cortisol or C-reactive protein levels between groups. All measurements were carried out in a blinded fashion. CONCLUSIONS: This study demonstrates that laparoscopic surgery appears to be associated with similar metabolic responses compared with open surgery, while immune parameters vary greatly between groups. The beneficial effects of laparoscopic surgery may relate, in part, to preservation of immune function in the postoperative period.

Adult↗
PubMed1994

Peritoneal aspiration cytology as a diagnostic aid in acute appendicitis.

A total of 110 consecutive patients presenting to one surgical firm with suspected acute appendicitis underwent peritoneal aspiration cytology. Aspiration was successful in 108 patients and 44 were positive. Patients with a positive result underwent emergency surgery; 42 had histologically proven acute appendicitis and two peritonitis of other causes. Seven patients with a negative result underwent appendicectomy; four had acute appendicitis and three a normal appendix. Peritoneal aspiration cytology had a sensitivity for acute appendicitis of 91 per cent and a specificity of 94 per cent. The positive predictive value of the test was 95 per cent and the negative predictive value 94 per cent. The negative appendicectomy rate was 10 per cent overall and 11 per cent in women of reproductive age. Peritoneal aspiration cytology is a useful diagnostic test in the management of patients with suspected acute appendicitis.

Acute Disease↗
PubMed1994

Lewis phenotype, secretor status, and coeliac disease.

Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leucocyte antigen (HLA) markers. This study investigated the possibility of an association with coeliac disease using red cell Lewis (Le) blood group phenotype to infer secretor status. Among 73 patients with coeliac disease who had Le a or b antigen, 48% were non-secretors (Le a + b-) compared with 27% of 137 blood donors (p = 0.004: odds ratio 2.49, 95% confidence intervals 1.37 to 4.51) and 26% of 62 medical and nursing staff controls (p = 0.014: odds ratio 2.65, 95% confidence intervals 1.27 to 5.50). Clinical characteristics did not differ between secretors and non-secretors with coeliac disease. Thus, the non-secretor state is significantly associated with coeliac disease, suggesting that genes on chromosome 19 may directly or indirectly participate in conferring susceptibility.

Celiac Disease↗
PubMed1994

Laparoscopic excision of a patent urachus.

We report the case of a patent urachus presenting as an umbilical discharge. The urachus was visualised laparoscopically, divided at either extremity, and successfully removed with subsequent abrogation of symptoms.

Adult↗
PubMed1993

The effect of hypoxia on propranolol clearance during antegrade and retrograde flow in the isolated perfused rat liver preparation.

We investigated, using the single-pass isolated perfused rat liver preparation, whether the centrilobular location of hepatic oxidative drug metabolism could be a contributing factor to the marked sensitivity of drug oxidation to hypoxia. Livers (N = 7) were each perfused for 130 min with 2 micrograms/mL (+)-propranolol, a drug metabolized almost entirely by oxidation in the rat. The direction of flow was reversed after 60 min, the order of flow direction being randomized. Normal oxygenation was used during the first 30 min of antegrade and of retrograde perfusion, but in the second 30 min perfusate was equilibrated with a N2/O2 mixture designed to reduce hepatic oxygen delivery by half. During normal oxygenation there was no significant difference between antegrade and retrograde perfusion in hepatic oxygen delivery and physiological parameters such as oxygen consumption and extraction, perfusion pressure and bile flow. During hypoxia, mean oxygen delivery was slightly lower with retrograde perfusion (retrograde: mean = 2.37 mumol/min/g liver, range = 1.56-3.17; antegrade: mean = 2.90 mumol/min/g liver, range = 1.96-4.08; P = 0.04), but there was no significant difference in physiological parameters within each liver (P > 0.05). Propranolol clearance during normal oxygenation was similar to the perfusion rate (10 mL/min) and was the same for both directions of perfusion (antegrade 9.88 +/- 0.07 mL/min, retrograde 9.88 +/- 0.13 mL/min, P > 0.05). Hypoxia reduced propranolol clearance substantially, but the decrease was significantly greater with antegrade perfusion (5.65 +/- 1.89 mL/min) than with retrograde perfusion (6.76 +/- 1.95 mL/min, P = 0.014). Oxidative drug metabolism is located primarily in the centrilobular zone and sinusoidal oxygen concentration is lowest in the "downstream" zone with both antegrade and retrograde perfusion. These findings suggest that the centrilobular location of propranolol metabolism may influence the effect of hypoxia on propranolol elimination, but is not a major contributor to the marked sensitivity of propranolol elimination to hypoxia antegrade perfusion.

Animals↗
PubMed1993

Correlation of peritoneal aspiration cytology with acute appendicitis.

Fifty-one patients in whom a clinical diagnosis of acute appendicitis had been made underwent peritoneal aspiration cytology (PAC). Thirty-six had a positive result, 11 had a negative result and aspiration failed in four cases. All patients had an appendicectomy and the histological findings were correlated with the PAC results. Thirty-five of the 36 patients with a positive PAC had histologically proven appendicitis. Seven of the 11 patients with a negative result had normal appendices. The sensitivity of PAC for acute appendicitis was 85% and the specificity was 70%. The positive predictive value was found to be 97% and the negative predictive value 60%. Peritoneal aspiration cytology is a useful aid in the diagnosis of acute appendicitis however, a negative result does not exclude this diagnosis.

Acute Disease↗
PubMed1993

Secretor status and Helicobacter pylori infection are independent risk factors for gastroduodenal disease.

The hypothesis that non-secretors of ABO blood group antigens, a group shown to be more susceptible to certain bacterial infections, may be at greater risk of gastroduodenal disease because of increased susceptibility to Helicobacter pylori infection was investigated. Of 101 patients with symptoms of dyspepsia who were undergoing endoscopy, 32% were non-secretors (determined from Lewis blood group phenotype), 36% had endoscopically visible gastroduodenal disease (antral gastritis, gastric ulcer, erosive duodenitis, duodenal ulcer or some combination), and 58% had H pylori detected in antral biopsy specimens. Non-secretors and patients with H pylori infection were significantly more likely to have gastroduodenal disease (p = 0.02 and p = 0.002 respectively). There was, however, no significant association between secretor status and H pylori infection, logistic regression analysis confirming that these were independently associated with gastroduodenal disease. Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors was 1.9 (95% confidence intervals 1.2, 3.2). Non-secretion of ABO blood group antigens is not related to H pylori infection but is independently and significantly associated with endoscopic gastroduodenal disease. The mechanism of this remains to be explained.

ABO Blood-Group System↗
PubMed1992

Detection of undiagnosed coeliac disease with atypical features using antireticulin and antigliadin antibodies.

Eighteen patients with a variety of non-gastrointestinal symptoms were incidentally found to have circulating antireticulin antibody and on subsequent testing were also positive for antigliadin antibody. They prospectively underwent jejunal biopsy to determine whether or not they had coeliac disease. Their age range was 21-79 years (mean 42 years). Enteropathy was present in 13 (72 per cent) and was always associated with circulating IgA antigliadin antibody. Enteropathy was not present in the five cases who had only IgG antibody. Clinical improvement occurred in eight of 11 patients who complied with a gluten-free diet and was paralleled by an improvement in the mucosal histology in seven of eight who were re-biopsied. The most remarkable cases were two patients who presented with severe debility and no apparent haematological or biochemical abnormalities, and who subsequently made a dramatic recovery on a gluten-free diet. It is concluded that antireticulin antibody detected by routine autoantibody screening and confirmed to have IgA antigliadin antibody specificity is a useful indicator of an otherwise undiagnosed enteropathy. This serves to emphasize that the condition can sometimes be associated with atypical features and significant morbidity.

Adult↗
PubMed1990

Circulating osteocalcin in primary biliary cirrhosis following liver transplantation and during treatment with ciclosporin.

Circulating osteocalcin, a non-collagen bone protein is considered a useful indirect index of turnover. Osteocalcin levels were measured by radioimmunoassay in 57 female patients with primary biliary cirrhosis (PBC) from two centres, 52 normal female controls, 11 female patients following liver transplantation for PBC and seven female patients with PBC treated with Ciclosporin. Serum levels were significantly less in the PBC group (median 10 ng/ml) compared to normals (median 15 ng/ml: p less than 0.001). Patients with PBC treated with Ciclosporin had significantly higher levels than untreated patients (median 23 ng/ml: p less than 0.001). Levels also increased significantly following transplantation when all patients were receiving Ciclosporin (median 40 ng/ml: p less than 0.001). The results suggest that the abnormal bone metabolism of PBC is significantly altered by Ciclosporin and liver transplantation.

Adrenal Cortex Hormones↗
PubMed1989

The frequency of gastrointestinal endocrine tumours in a well-defined population--Northern Ireland 1970-1985.

The reported incidence of gastrointestinal endocrine tumours is variable. In Northern Ireland circumstances allowing such an assessment are favourable with a central diagnostic laboratory and register established to collect data on tumours from a well-defined population of 1.5 million people. From 1970 to 1985, 368 cases were recorded of which 85 per cent were carcinoid tumours. The annual incidence of carcinoid tumours was 1.3 per 100,000 of the population and the majority occurred in the appendix (61 per cent). No patients presented with the carcinoid syndrome. The annual incidence for other tumours was 0.12 per 100,000 for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellison syndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05. There were two cases of VIPoma, one glucagonoma, one neurotensinoma and one tumour producing ACTH. It is possible that some tumours are more uncommon than others because of difficulty in diagnosis.

Adenoma, Islet Cell↗