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Biomedical subjects

S J Middleton

Publications and source records attributed to S J Middleton.

At least 37 records · Page 2Linked to original sources
PubMed1997

An indirect means of assessing potential nutritional effects of dietary olestra in healthy subgroups of the general population.

The potential for olestra to affect the absorption of dietary components was measured in 18- to 44-y-old humans and the weanling pig. Results from the studies were assessed to determine if they were relevant to subgroups of the population not included in the studies. Hypothetrically, two factors that might cause the study results not to be relevant to certain subgroups are dietary pattern and metabolic need. A dietary pattern resulting in olestra-to-nutrient intake ratios greater than those tested in the studies might produce effects greater than those measured. Metabolic needs (i.e., nutrient requirements) among subgroups greater than those of the study population might mean that any effects on nutrient absorption seen in the studies would be larger among subgroups. If olestra-to-nutrient ratios and nutrient requirements of a subgroup were less than those covered in the studies, then the effects of olestra on the nutritional status of the subgroup should be no different than the effects measured in the studies. Subgroups with high olestra-to-nutrient intake ratios were identified by calculating the ratios for those nutrients assessed in the studies [i.e., macronutrients, vitamins A (including beta-carotene), D, E and K, folate, vitamin B12, calcium, iron and zinc]. Subgroups with the greatest olestra-to-nutrient intake ratios for one or more nutrients included children, teenagers and young adults, women from low income families and vegetarians. Subgroups with the greatest metabolic need for one or more nutrients included children, teenagers, and pregnant and lactating women. The olestra-to-nutrient ratios and nutrient requirements of the subgroups having the greatest ratios and requirements were compared with those of the test population. The olestra-to-nutrient intake ratios fed in the studies were greater than those for any subgroup for all nutrients except calcium, which is not affected by olestra. Metabolic needs of the test population were greater than those of all population subgroups for all nutrients. The effects of olestra on nutritional status should not be different or greater than those measured in the controlled clinical tests for subgroups not directly tested.

Adolescent↗
PubMed1997

Assessment of the nutritional effects of olestra, a nonabsorbed fat replacement: summary.

Olestra is a zero-calorie fat replacement intended to replace 100% of the fat used in the preparation of savory snacks. Olestra can affect the absorption of other dietary components, especially highly lipophilic ones, when ingested at the same time. The potential effects of olestra on the absorption of essential fat-soluble and water-soluble dietary components have been investigated in pigs and in humans. In these studies, subjects were fed daily amounts of olestra up to 10 times the estimated mean intake from savory snacks and the olestra was eaten each day of the studies. In real life, snacks are eaten on average five times in a 14-d period. Olestra did not affect the availability of water-soluble micronutrients or the absorption and utilization of macronutrients. Olestra reduced the absorption of fat-soluble vitamins A, D, E and K; however, the effects can be offset by adding specified amounts of the vitamins to olestra foods. Olestra also reduced the absorption of carotenoids; analysis of dietary patterns showed that in real life the reduction will likely be <10%. Any effect on vitamin A stores caused by a reduction in carotenoid uptake is offset by the addition of vitamin A to olestra foods. Because of the olestra-to-nutrient ratios fed and the nutritional requirements of the test subjects, the effects of olestra on nutritional status of subgroups of the population are unlikely to be different than those measured in the studies. An analysis of lipophilicity showed that olestra is unlikely to significantly affect the uptake of potentially beneficial phytochemicals from fruits and vegetables. Some people eating large amounts of olestra snacks may experience common GI symptoms such as stomach discomfort or changes in stool consistency, similar to symptoms accompanying other dietary changes. These symptoms present no health risks.

Animals↗
PubMed1997

Confirmation of nitric oxide synthesis in active ulcerative colitis by infra-red diode laser spectroscopy.

BACKGROUND: The synthesis of nitric oxide (NO) in the colonic mucosa of patients affected by ulcerative colitis (UC) has been previously investigated using indirect measurements of enzyme activity and non-specific measurements of luminal NO gas. The aim of this study was to determine unequivocally if luminal NO gas in active UC is present in greater concentrations than in healthy control subjects. METHODS: Luminal gas was collected from eight patients with active UC and eight healthy volunteers. NO gas concentration was measured using diode laser spectroscopy. RESULTS: NO gas was detected in four of eight patients with active UC (range 0.13-1.1 nmol) and none of the healthy control subjects. CONCLUSION: NO gas is present in greater concentrations in patients with active UC than in control subjects. This supports the view that mucosal NO synthesis is increased in ulcerative colitis.

Colitis, Ulcerative↗
PubMed1997

Olestra, a nonabsorbed, noncaloric replacement for dietary fat: a review.

Olestra has been shown to be safe for its intended use by extensive testing in animals and in humans. It is not digested or absorbed and has no effect on the structure or physiology of the GI tract, the only organ of the body that it contacts. Olestra can interfere with the absorption of other lipophilic substances from the GI tract. The interference occurs because a portion of those molecules that are sufficiently lipophilic partition into the nonabsorbed olestra and is carried out of the body. Whether olestra will interfere with the absorption of a specific molecule can be predicted from the octanol-water partition coefficient of the molecule, a parameter that can be measured or calculated from a knowledge of the structure of the molecule. Olestra does not affect the absorption or efficacy of oral drugs because, in general, they are not sufficiently lipophilic to partition into the olestra. Olestra does not affect the absorption of water-soluble micronutrients or the absorption and utilization of macronutrients. Olestra can reduce the absorption of the fat-soluble vitamins when olestra foods and the vitamins are coingested. These effects can be offset by adding specific amounts of the vitamins to foods made with olestra. Other than the carotenoids and vitamins A and E, olestra does not affect the absorption of potentially beneficial components of fruits and vegetables. The effects on the vitamins can be offset by adding the vitamins to olestra foods. The reduction in the absorption of carotenoids will be less than 6-10% when olestra snacks are eaten under free-living dietary patterns. Any effect this reduction has on vitamin A status can be offset by addition of vitamin A to the foods. The absorption of flavonoids, polyphenols, and most other phytochemicals in fruits and vegetables, which have been shown to provide beneficial health effects, will not be affected by olestra because they are not sufficiently lipophilic. Individuals consuming large quantities of olestra may experience mild or moderate common GI symptoms such as loose or soft stools, gas, or nausea, symptoms similar to those experienced with certain other foods or changed dietary habits. When olestra snack foods are eaten under free-living dietary patterns, the symptoms are not different from those experienced when eating full-fat snack products, in either incidence or severity. When they are experienced, the symptoms resolve in 1-2 days, but may recur. They do not worsen with continued or increased olestra consumption and pose no health risk to the consumer. Olestra products will carry an information label alerting consumers to the possibility of GI symptoms. Olestra foods provide an additional option to those individuals who want or need to lower their total energy intake and body weight. These individuals will find it easier to change dietary habits and to maintain healthful nutritional practices when they use olestra foods. For those who want or need to reduce fat intake but not lose weight, olestra foods can reduce fat intake without affecting energy. Because olestra foods have taste and other organoleptic properties that are similar to those of full-fat foods, individuals will find it easier to switch to low-fat diets.

Animals↗
PubMed1995

Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn's disease.

Elemental diets are effective treatments for active Crohn's disease. To determine which dietary constituents are of therapeutic importance, the effectiveness of four separate feeds was related to their compositions, and the findings substantiated by meta-analysis of previous dietary studies. 76 patients with active Crohn's disease were recruited. 17 were randomised to an amino acid-based elemental diet (E028), 22 to E028 with added long-chain triglyceride (E028 LCT), 18 to a semi-elemental, peptide based diet (Pepdite 2+) and 19 received E028 with added medium-chain triglyceride (E028 MCT). Disease activity fell in all groups and remission rate was negatively correlated with the amount of energy derived from LCT (r = -0.97, p = 0.016). Inflammatory indices fell in the groups (E028 + E028 MCT) containing least LCT. No other dietary constituents correlated with remission rate. A meta-analysis of published studies confirmed a negative correlation between remission rate and LCT (r = -0.63, p = 0.006) but not other constituents. The association between dietary LCT and remission rate may have pathogenic significance and allow the development of more effective enteral feeds.

Journal Article↗
PubMed1995

The effects of aminosalicylic acid derivatives on nitric oxide in a cell-free system.

AIMS AND METHODS: To determine the effect of aminosalicylic acid derivatives on the concentration of nitric oxide produced in a cell-free system, by the use of a sensitive and specific polarographic meter. RESULTS: The aminosalicylic acid derivatives 3-ASA (IC50 100 microM), 4-ASA (IC50 350 microM) and 5-ASA (IC50 5 microM) all decreased the nitric oxide signal. These drugs had a similar inhibitory effect on the formation in vitro of nitrite from sodium nitroprusside (IC50: 200 microM, 500 microM and 100 microM, respectively). Sulphasalazine (31.1 +/- 5% decrease in signal at 1 mM) was less effective than 5-ASA, but sulphapyridine, N-acetyl 5-ASA, indomethacin and hydrocortisone produced no decrease in nitric oxide signal at all. CONCLUSIONS: Nitric oxide binding may be part of the mechanism by which ASA derivatives exert their therapeutic effect, and this work suggests that it may be an important factor in the pathogenesis of ulcerative colitis.

Aminosalicylic Acids↗
PubMed1995

Validation of 99Tcm-HMPAO leucocyte scintigraphy in ulcerative colitis by comparison with histology.

Leucocyte scintigraphy offers an alternative to more invasive techniques in the investigation of inflammatory bowel disease. The accuracy of 99Tcm-HMPAO leucocyte scintigraphy has not been assessed by comparison with colonic histology, which was the aim of this study. 15 patients with ulcerative colitis underwent 99Tcm-HMPAO leucocyte scintigraphy (TLS) less than 5 days before colonoscopy. Histological features of mucosal biopsies were compared with total and segmental colonic TLS scores. Segmental and total scintigraphy scores correlated most strongly with histological grades for acute inflammation (r = 0.75, p < 0.001 and r = 0.9, p < 0.001, respectively) and chronic inflammatory cell infiltration in the lamina propria (r = 0.76, p < 0.001 and r = 0.86, p < 0.001, respectively). 99Tcm-HMPAO leucocyte scintigraphy detected acute inflammation in the colon of patients with ulcerative colitis with a sensitivity of 91% and negative predictive value of 80% and localized acute inflammation to a particular colonic segment with a sensitivity of 82%, specificity of 94%, accuracy of 88%, positive predictive value of 94% and negative predictive value of 91%. 99Tcm-HMPAO leucocyte scintigraphy positivity predicts and localizes colonic acute inflammation with a high degree of confidence, but negative scintigraphy does not exclude acute inflammation.

Adult↗
PubMed1993

Increased nitric oxide synthesis in ulcerative colitis.

Nitric oxide (NO) is produced in tissues by NO synthase with the liberation of equimolar amounts of citrulline. Citrulline concentrations were significantly higher in rectal biopsy specimens from patients with active ulcerative colitis than in those from patients with quiescent disease or with normal histology. Incubation of biopsy samples from patients with ulcerative colitis with NG-monomethyl-L-arginine (L-NMMA) inhibited citrulline production. These findings suggest that mucosal NO biosynthesis is increased in active colitis and that NO may have a pathogenic role in ulcerative colitis.

Amino Acids↗
PubMed1993

Nitric oxide affects mammalian distal colonic smooth muscle by tonic neural inhibition.

1 The role of the L-arginine-nitric oxide (NO) pathway in tonic neural inhibition of spontaneous mechanical activity of distal colonic circular smooth muscle (DCCSM) was investigated in male Wistar rats. 2 Muscle strips were mounted in organ baths and spontaneous contractions recorded with isometric force transducers. They were characterized as low frequency (LFCs) 0.41 +/- 0.03 N cm-2 or high frequency contractions (HFCs) 0.22 +/- 0.04 N cm-2. The latter occurred intermittently to produce summation contractions (SCs) range 0.5-12 N cm-2. 3 Tetrodotoxin (100 nM) increased the forces of LFCs and SCs. Increase in force to tetrodotoxin did not occur after incubation of the muscle with NG-monomethyl-L-arginine (L-NMMA) 500 microM, an inhibitor of NO biosynthesis. 4 L-NMMA but not its enantiomer D-NMMA increased the force of LFCs (EC50: 200 microM) and SCS (EC50:175 microM) in a concentration-dependent manner which was reversed by L-arginine but not by D-arginine. 5 Muscle, precontracted by acetylcholine, relaxed to sodium nitroprusside (EC50:1.8 microM) NO gas (EV50:70 microliters) and NO solutions (EC50:4 microM) in a concentration-dependent manner. Guanosine 3':5'-cyclic monophosphate tissue concentrations (pmol mg-1 protein) were elevated in muscle after relaxation by sodium nitroprusside (500 microM) from 0.32 +/- 0.06 to 1.2 +/- 0.37 and by 1 ml of NO gas from 0.49 +/- 0.05 to 1.54 +/- 0.14. 6 These data suggest that DCCSM is under tonic neural inhibition mediated by NO biosynthesis.

Acetylcholine↗
PubMed1993

Relaxation of distal colonic circular smooth muscle by nitric oxide derived from human leucocytes.

The role of nitric oxide (NO) as a mediator of colonic circular smooth muscle relaxation by human leucocytes was investigated. Granulocytes and mononuclear cells were obtained by gradient centrifugation of venous blood from healthy volunteers. Both cell types relaxed precontracted distal colonic circular smooth muscle in a concentration dependent manner. Muscle relaxation was inhibited by preincubation of cells with NG-monomethyl-L-arginine (100 microM/l) but not by preincubation with NG-monomethyl-D-arginine (100 microM/l). Muscle relaxation by cells was reduced by 200 nM oxyhaemoglobin and 10 microM methylene blue but was increased by 60 units/ml superoxide dismutase. Non-viable cells did not produce muscle relaxation. Activation of mononuclear cells by incubation with 100 nM/l FMet-Leu-Phe increased muscle relaxation, whereas activation of granulocytes did not. Granulocytes and mononuclear cells relax precontracted distal colonic circular smooth muscle in vitro by the release of NO that may contribute to motility disorders of the gut associated with inflammation.

Adult↗
PubMed1992

Postprandial lipid response following a high fat meal in rats adapted to dietary fiber.

Rats were adapted to diets containing 5 g/100 g cellulose (CL), 5 g/100 g oat bran fiber (OB) or 5 g/100 g psyllium husk (Psy) for 4 wk. Following a 12-h fast, animals were either killed at 0 h (baseline) or fed 4.5 g of a test meal that provided 50% energy from fat, then killed at 1, 4 or 6 h postprandially. Fasting plasma and HDL cholesterol concentrations were lower in Psy-fed animals than in rats fed either CL or OB. Plasma triglycerides increased significantly from baseline (0 h) in all groups but did not differ among diet treatments. Increases in triglyceride content of the treatments. Increases in triglyceride content of the chylomicron/VLDL fraction occurred in the CL- and OB-fed groups and in the HDL fraction of the Psy-fed group during the postprandial period. In unfed animals the hepatic and intestinal levels of apolipoprotein A-IV mRNA were higher in the CL-fed group than in the groups fed OB and Psy. Apolipoprotein B mRNA was higher in the intestine of the OB-fed group than in the groups fed CL and Psy and had a significant gradient along the small intestine, increasing in the distal third. The results suggest that chronic consumption of fiber is less likely to modify the acute plams triglyceride response to a fat-containing test meal than if a fiber supplement is incorporated into the meal.

Animals↗
PubMed1992

99Tcm and 111In leucocyte scintigraphy in inflammatory bowel disease.

A comparative study of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and 111In leucocyte scintigraphy was performed in inflammatory bowel disease. Two hundred and thirty-four patients were studied, 146 had 99Tcm-HMPAO, 82 had 111In and six had both. The sensitivity, specificity and accuracy of the 99Tcm leucocyte scan were 96, 97 and 97%, respectively, and 96, 97 and 97%, respectively, for the 111In leucocyte scan. 99Tcm-HMPAO leucocytes demonstrated similar diagnostic accuracy to 111In-labelled leucocytes with improved image quality and reduced radiation dose.

Adolescent↗
PubMed1992

The role of faecal Candida albicans in the pathogenesis of food-intolerant irritable bowel syndrome.

Candida albicans was sought in stool samples from 38 patients with irritable bowel syndrome and 20 healthy controls. In only three patients with irritable bowel syndrome was C. albicans discovered and these patients had either recently received antibiotics or the stool sample had been delayed more than 24 hours in transit. C. albicans was isolated from none of the control stool samples. We conclude that C. albicans is not involved in the aetiology of the irritable bowel syndrome.

Candida albicans↗
PubMed1991

Impending paradoxical embolism: a rare but important diagnosis.

A man aged 50 presented with a history of a cerebrovascular accident and arterial embolism at two discrete peripheral sites. Echocardiography showed thrombus trapped in an interatrial site and impending paradoxical embolism was diagnosed. Treatment with heparin was started and the potentially embolic intracardiac material was removed at open heart surgery. The patient was treated with warfarin and made a good recovery. This is only the third case report of impending paradoxical embolism diagnosed in life.

Echocardiography↗
PubMed1990

Haemorrhagic pancreatitis--a cause of death in severe potassium permanganate poisoning.

Severe potassium permanganate poisoning (more than 10 g of potassium permanganate) is invariably associated with massive systemic upset and death. Multiple organ damage has been recognized as an inevitable consequence of such an overdose, although pancreatitis has not been previously reported. Death due to cardiovascular collapse and profound hypotension is a common end point in those who reach hospital, but the pathogenesis is uncertain. We report a case of haemorrhagic pancreatitis following an overdose of potassium permanganate and suggest that this complication may be an unrecognized factor contributing to the extremely high mortality rate associated with this condition.

Acute Disease↗