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Biomedical subjects

S M Greenfield

Publications and source records attributed to S M Greenfield.

At least 19 recordsLinked to original sources

Drinking before endoscopy: milk or water?

BACKGROUND: The traditional fluid fast prior to endoscopy is unnecessary. We have previously shown that drinking water prior to endoscopy does not affect either the quality of mucosal views or residual gastric fluid volumes when compared to patients undergoing endoscopy after a standard fast. The present study was designed to establish whether milk, which may delay gastric emptying, could also be drunk prior to endoscopy without adverse effect. METHODS: Forty-eight patients (mean age 48 years, range 20 to 79) undergoing routine upper gastrointestinal endoscopy after overnight fast were randomized to drink 200 ml of either still mineral water or full fat milk. Endoscopy was performed 90 minutes later, when all residual gastric fluid was aspirated via the endoscope. Volume and pH of gastric aspirate were measured and the quality of the mucosal view at endoscopy recorded as poor, adequate, or excellent. RESULTS: No difference was shown between water (n = 27) and milk (n = 21) drinkers in residual gastric volume (mean +/- SEM, water vs milk) (16.0 ml +/- 1.5 vs 18.9 ml +/- 2.9) or pH (2.23 +/- 0.14 vs 2.48 +/- 0.14). Of those patients with poor, adequate, or excellent views, 4 of 4, 11 of 12, and 6 of 32 patients, respectively, were milk drinkers (chi-squared test for trend = 21.7, df = 1, p < 0.001), indicating significantly worse mucosal views in the group drinking milk. CONCLUSION: Drinking water up to 90 minutes prior to endoscopy is safe, but milk should be discouraged because of suboptimal mucosal views.

Animals

A qualitative investigation into why patients change their GPs.

BACKGROUND: In the past patients have rarely changed doctor. The UK Government has made such change easier and it appears to be becoming more common. Changing doctor without changing address may be indicative of dissatisfaction with the GP service. Previous research in this area has been largely quantitative. OBJECTIVE: To identify why patients change their GP although they have not moved house. METHOD: Qualitative investigation of patients' experiences. In depth interviews of 24 patients were conducted to determine why they had left their previous doctor. Letters describing the process of change were received from a further 17 patients. Analysis was performed using standard qualitative techniques. RESULTS: The decision to change was in most cases multi-factorial. Interviews yielded more detailed and richer accounts than letters. For interviewees, rudeness or the attitude of the doctor was the commonest reason. Overall, 19 different reasons, in four categories, were identified. The largest single category was accessibility, closely followed by attitudinal problems. Clinical issues and personal characteristics of the doctor were less common. The majority of those responding by letter gave only one reason, usually distance. CONCLUSION: Patients change doctor after careful consideration and commonly for interpersonal reasons. There is usually one critical factor in the decision to change. Factors may be modifiable or non-modifiable. Critical event audit may enable GPs to analyse the reasons why patients leave their lists.

Adult

Acquisition of basic clinical skills in the general practice setting.

Undergraduate medical education in the UK is changing due to both education pressure (from the General Medical Council) and changes in the hospital service. As a result the role of general practice in providing core clinical experience is under debate. The purpose of this study was to determine the clinical contact available for junior clinical medical clerks (third year) attached to five general practices. We report here on the clinical experience recorded by students during 106 sessions (74% of possible sessions). One hundred and one patients were seen, 54% females; ages ranging from 14 to 92. Four hundred and twenty-six symptoms were recorded; the largest category (36%) was CVS/respiratory followed by neurological (20%). Shortness of breath was the commonest single symptom (46% in the CVS/respiratory category). Three hundred and seventy-one signs were recorded; 48% were in the CVS/respiratory category, 33% in the neurological category. Cardiac murmurs were the commonest single sign (34% of the CVS/respiratory category). Sixty-nine separate comments were made by students about the range of clinical experience available; all were favourable. Forty-eight per cent of comments highlighted the availability of patients with appropriate symptoms and signs. This study has demonstrated that general practices can provide appropriate clinical exposure which complements hospital teaching for junior students.

Adolescent

A national survey to medical and dental schools to assess the level of undergraduate teaching and research about HIV/AIDS in the UK.

The views of heads of academic departments in UK medical and dental schools on the extent of their specialty's involvement in teaching undergraduates about HIV/AIDS and undertaking research in this area was ascertained by postal questionnaire. Three hundred and nineteen responses were received from medical schools (61.7%) and 58 responses from dental schools (53.2%). The greatest number of responses in one specialty was received from the Departments of General Practice, Paediatrics and Children's Dentistry. The amount of teaching varied widely, was dispersed throughout the curriculum within a wide range of broader subject areas and tended to be carried out by senior staff using didactic lecture format. Dental courses were more often assessed than medical courses. The small number of patients available was seen as a major problem. Involvement in research was appreciable. However, knowledge of student awareness campaigns was not widespread. We conclude that more specific teaching on HIV/AIDS is needed, particularly discussion about attitudes towards patients and ethical issues. HIV/AIDS counsellors should have an increased involvement in undergraduate teaching and teaching methods should provide opportunities for interactive discussion. Extensive research is being conducted in the UK. However, further work is needed to identify the perceived needs of students and the extent to which these are being met.

Acquired Immunodeficiency Syndrome

Assessment of residual gastric volume and thirst in patients who drink before gastroscopy.

BACKGROUND: Before endoscopy patients undergo an uncomfortable fluid fast to reduce the risk of gastric acid aspiration and to ensure good endoscopic views are obtained. However, fluids rapidly leave the stomach and thus a long fluid fast before endoscopy may not be required. AIMS: The object of this study was to establish whether drinking before endoscopy is safe and relieves patients' symptoms of thirst. PATIENTS AND METHODS: 88 patients with American Society of Anaesthesiologists classification of physical status grades I and II were recruited in a controlled randomised single blind trial. The volume and pH of gastric aspirate obtained at gastroscopy was assessed in patients who drank 330 ml of water a minimum 90 minutes before their endoscopy and compared with values in patients who starved overnight. RESULTS: 44 patients who drank ('drinkers') 330 ml of water a mean 117 minutes before their morning gastroscopy had a similar volume and pH of gastric aspirate compared with 44 patients starved overnight ('starvers'); median volume 12.5 ml versus 10 ml, median pH 2.0 versus 2.0; 'drinkers' versus 'starvers' (NS). Before endoscopy patients were asked to score their thirst and hunger ratings as either none, mild, moderate or severe. Ratings for moderate and severe thirst were grouped together for analysis. The percentage of drinkers compared with starvers in each group with no thirst, mild thirst, and moderate severe thirst was 63%, 46%, and 37% respectively (chi 2 test for trend p < 0.05). Hunger ratings were similar in the two groups. CONCLUSIONS: It is safe for elective day cases to drink a significant volume of water two hours before endoscopy and this alleviates symptoms of thirst.

Adult

Assessment of toxic metal exposure following the Camelford water pollution incident: evidence of acute mobilization of lead into drinking water.

Following the incident of acidic pollution of water by aluminium sulfate centred around Camelford in July 1988, we have carried out a retrospective analysis of the mobilization of toxic metals to residents of the area. An advanced nuclear technique was used to measure trace levels of elements within hair, thus, avoiding surface contamination. In contrast to controls, lead, but no other toxic metals, was consistently found within sections of hair that dated to mid-1988 from four residents; they must, therefore, have consumed this metal around the time of the incident. The source of this lead was probably local water pipe residue, and this was found on analysis to have a matrix specific to such soft-water areas that, prior to the incident, had slowly accumulated certain toxic metals such as cadmium and uranium and particularly lead. Lead is mobilized from such residues by acidic water and could, therefore, have heavily contaminated mains water after the incident. However, analyses of residents' plasma and whole blood, and of urine following a lead-chelation test, showed no evidence of either long-term increased body burdens of toxic metals or depletion of essential elements. In addition, we found no evidence of continued poor water quality in the area. In conclusion, during a short period following the pollution, some residents who consumed mains water would have been acutely exposed to lead and other toxic metals. Prediction of the scale of metal exposure to individuals was not possible owing to heterogeneity of the water distribution network, but long-term effects to residents from lead are not anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption

Omeprazole and dry mouth.

BACKGROUND: Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy. METHODS: We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes. RESULTS: Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus. CONCLUSION: Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous.

Aged

Lipid peroxidation in rats chronically fed ethanol.

Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free radical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of equal male: female ratio (n = 24) were fed alcohol by gavage twice daily to achieve a dosage of 15 g/kg body weight. Mean peak blood alcohol concentrations of 186 mg% were produced in males and 156 mg% in females. The animals were allowed free access to standard laboratory chow and water. Control animals were pair-fed to the alcoholic group and fed isocaloric glucose by gavage. Groups of animals were killed between 9 and 11 am on consecutive mornings, after nocturnal feeding, since it has previously been shown that fasting rapidly depletes hepatic glutathione concentrations. Hepatic glutathione was measured by a spectrophotometric enzymatic recycling procedure. As a marker of lipid peroxidation hepatic malonaldehyde (MDA) was measured by high performance liquid chromatography. Hepatic MDA was increased in the alcoholic group (p < 0.001), as was total hepatic glutathione (p < 0.0001). Plasma concentrations of alpha-tocopherol were increased in the alcoholic group, but ascorbic acid and superoxide dismutase values were not affected. No sex differences were detected. The increased MDA production in the alcohol group is strong evidence that lipid peroxidation is a mechanism of alcoholic tissue damage. The rise in hepatic glutathione may be an adaptive response to free radical production that protects the rat against tissue damage.

Animals

Comparison of serum procollagen III peptide concentrations and PGA index for assessment of hepatic fibrosis.

In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs and to reduce the need for liver biopsy.

Apolipoprotein A-I

Gastro-intestinal availability of aluminium from tea.

The in vitro speciation of aluminium (Al) in black tea infusion (pH 4.8) was assessed using 3000, 10,000 and 30,000 Da cut-off ultrafilters, and the effect of adding human gastric juice (pH 2.3) and then raising the pH to 6.5 were also studied. 78% Al in the tea infusion passed through the 3000-Da ultrafilter; this percentage increased to more than 90% with the addition of gastric juice at pH 2.3, but then reduced to approximately 5% when the incubate was adjusted to pH 6.5. The breakdown of tea-derived polyphenols to low molecular weight phenols in vivo was measured using high-resolution 1H nuclear magnetic resonance spectroscopic analysis of ileostomy effluent, but there was no evidence of low molecular weight breakdown products from the polyphenols of ingested tea in this effluent. These results suggest that only a small proportion of Al in tea is potentially available for absorption throughout the small bowel. It may be misleading to estimate systemic Al absorption from tea drinking simply from total urinary aluminium excretion as has been done previously.

Aluminum

Effect of thyroidectomy and adrenalectomy on changes in liver glutathione and malonaldehyde levels after acute ethanol injection.

At low concentrations ethanol is metabolized largely by alcohol dehydrogenase to acetaldehyde, while at higher concentrations a microsomal ethanol oxidising system (MEOS) is involved, namely cytochrome P450 IIE1, which also probably generates free radical species. In hyperthyroidism hepatic glutathione stores are depleted and net superoxide anion production occurs. In contrast, in hypothyroidism hepatic glutathione may be increased and thus renders the liver less sensitive to alcohol generated free radical production. Steroid hormones inhibit lipid peroxidation. Sixty male Wistar rats either underwent thyroidectomy, adrenalectomy, or sham procedures. Twenty control animals were pair fed with thyroidectomized animals, whilst another twenty fed ad libitum. An intraperitoneal injection of alcohol (75 mmol/kg) was given 2.5 h prior to sacrifice to half the animals in each group, the remainder receiving saline. The total hepatic glutathione contents of the pair fed and the ad libitum groups were not different, but were significantly increased by thyroidectomy (p = < 0.001). This effect was significantly reduced by alcohol (p < 0.01). The sham procedures and dietary restrictions had no effect. The ethanol alone reduced total hepatic glutathione, but this only reached statistical significance in the thyroidectomized and sham-adrenalectomized groups. Hepatic malonaldehyde (MDA) levels were significantly reduced in the thyroidectomy group but alcohol had no effect on them. We conclude that hypothyroidism increased hepatic glutathione status, presumably by reducing radical production by enzyme systems, which would otherwise consume this important scavenger. Long term exposure to ethanol with induction of MEOS is probably required for it to generate toxic levels of free radical species.

Adrenal Glands

A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis.

In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four-fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.

Aged

Review article: the mode of action of the aminosalicylates in inflammatory bowel disease.

Sulphasalazine and other 5-aminosalicylic acid (5-ASA)-containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin-1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease. The effects of these drugs on prostaglandin production are more contentious, but it appears that 10(-5) to 10(-4) M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B4, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.

Aminosalicylic Acids

Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine.

The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.

Adult

Amaurosis fugax, Crohn's disease and the anticardiolipin antibody.

Crohn's disease is associated with a hypercoagulable state due to platelet or clotting abnormalities which may be responsible for the thromboembolic episodes seen in this condition. We report the occurrence of anticardiolipin antibodies in a patient with Crohn's disease who presented with Amaurosis fugax and suggest that these antibodies may be a further cause of the hypercoagulable state of Crohn's disease in some patients.

Aged

The effects of sulphasalazine and its metabolites on prostaglandin production by human mononuclear cells.

Although it has been proposed that sulphasalazine (SASP) and its metabolite 5-aminosalicylic acid (5-ASA) act therapeutically by inhibiting production of vasoactive and immunoregulatory prostaglandins (PGs), in previous in vitro studies these drugs have both inhibited and promoted PG production. This study demonstrates that SASP and 5-ASA promote or inhibit peripheral blood mononuclear cell PG production depending upon the PG measured, the concentration of the drug, and whether the cells were stimulated. Sulphapyridine, the other constituent of SASP, only inhibited production. At high concentrations of SASP and 5-ASA the viability of mononuclear cells was reduced. The enhancement of PG production and toxicity was greater with SASP than 5-ASA, while the PGs most affected by SASP were not those most affected by 5-ASA. Thus, in vitro SASP may possess properties other than those of 5-ASA and this may explain the different therapeutic properties of these two compounds.

Aminosalicylic Acids