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Biomedical subjects

P G Frost

Publications and source records attributed to P G Frost.

At least 19 recordsLinked to original sources

Wheat bread supplemented with depolymerized guar gum reduces the plasma cholesterol concentration in hypercholesterolemic human subjects.

Recent human studies have shown that the physiologic effects of guar gum are not diminished by partial depolymerization of its galactomannan fraction. We evaluated the effect of depolymerized guar galactomannan on fasting plasma cholesterol and triacylglycerol concentrations in healthy volunteers with moderately raised plasma cholesterol concentrations (range: 5.2-8.0 mmol/L). This study was designed as a randomized, double-blind crossover of two 3-wk feeding periods separated by a 4-wk washout period. Control and guar wheat breads were prepared by a commercial bread-making process. Subjects (n = 11) were asked to replace their normal bread with that provided, receiving control bread for one 3-wk period and guar bread for the other period, without altering their baseline diet. Subjects recorded their intake of foods for 6 consecutive days on three occasions during the study. Fasting venous blood samples (10 mL) were taken from subjects on two consecutive mornings at the start and end of each feeding period. No significant changes in body weight or dietary intake were recorded in the control and guar bread periods. There was a significant reduction (10%) in total plasma cholesterol concentration after the guar treatment (P < 0.001), mainly because of a reduction in the low-density-lipoprotein-cholesterol fraction. No changes in plasma high-density-lipoprotein-cholesterol or triacylglycerol concentrations were seen. The cholesterol-lowering effect of partially depolymerized guar gum appears to be of a magnitude similar to that of high-molecular-weight guar gum used in earlier studies.

Adult

Indian herbal remedies for diabetes as a cause of lead poisoning.

Herbal remedies from the Indian subcontinent have been found to have high concentrations of heavy metals and unsupervised treatment may result in toxicity. We report the case of an Indian patient with hepatitis who was found to have lead poisoning where the source was traced to ethnic remedies he had been taking for diabetes.

Adult

Bedside measurement of creatine kinase to guide thrombolysis on the coronary care unit.

Thrombolysis is effective in treating patients with acute myocardial infarction when started within 12 h of onset, and thus is in widespread use. Early diagnosis is essential but some patients admitted to the coronary care unit with myocardial infarction do not meet the diagnostic criteria on arrival, and thus do not undergo thrombolysis. We studied 117 patients admitted consecutively to our coronary care unit with suspected but unproven myocardial infarction; normally none would have received thrombolytic agents. In each patient creatine kinase levels were measured on admission and after intervals by nurses using capillary blood samples and a dry chemistry system. Infarction was subsequently confirmed in 29 patients. Of these, 17 (59%) were correctly diagnosed and underwent thrombolysis within 12 h on the basis of a raised creatine kinase measured at the bedside. Our findings suggest that use of a bedside assay by nurses allows additional patients with myocardial infarction to receive the benefit of thrombolytic therapy within the first 12 h.

Clinical Enzyme Tests

Simultaneous determination of vitamins A and E and carotenoids in plasma by reversed-phase HPLC in elderly and younger subjects.

A reversed-phase high-performance liquid-chromatographic method for the simultaneous determination of retinol, alpha-tocopherol, alpha-carotene, beta-carotene, cryptoxanthin, lutein/zeaxanthin, and lycopene is described. This method was applied to plasma measurements in healthy young and elderly subjects. The plasma, deproteinized with ethanol, is extracted twice with n-hexane. After evaporation, the residue is dissolved in 50 microL of tetrahydrofuran and made up to 200 microL with ethanol. Samples (50 microL) are injected onto a 250 x 4.6 mm column of 5-microns-particle Spherisorb ODS1 (Phase Separations) that had been equilibrated with solvent mixture A:B (90:10 by vol) [A = 100 mmol/L ammonium acetate in methanol: acetonitrile (80:20 by vol) and B = 100 mmol/L ammonium acetate in water] at 2 mL/min. The analytes are eluted by running a 12-min linear gradient to 100% A; solvent A is then maintained for 10 min. Intrabatch CVs were 2.3%, 3.3%, 2.8%, 3.6%, 3.6%, and 3.0% for retinol, alpha-tocopherol, lutein/zeaxanthin, cryptoxanthin, lycopene, and beta-carotene, respectively. The corresponding interbatch CVs were 4.9%, 5.8%, 12.3%, 6.5%, 8.0%, and 3.4%.

Adult

Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease.

In a case/control study, serum concentrations of vitamins A and E and major carotenoids were determined in patients with Alzheimer's disease, multi-infarct dementia and control subjects. The results showed that both Alzheimer's and multi-infarct dementia patients had significantly lower levels of vitamin E and beta-carotene than controls (vitamin E: 18.65 +/- 3.62 mumol/l in Alzheimer's disease and 15.80 +/- 6.93 mumol/l in multi-infarct dementia versus 30.03 +/- 12.03 mumol/l in controls; beta-carotene less than 0.13 to 0.42 mumol/l in Alzheimer's disease and less than 0.13 to 0.30 mumol/l in multi-infarct dementia versus 0.13 to 1.53 mumol/l in controls). Vitamin A was significantly reduced only in the Alzheimer's patients (1.56 +/- 0.78 mumol/l in Alzheimer's disease versus 2.13 +/- 0.86 mumol/l in controls).

Aged

Glycine nitrogen in total parenteral nutrition: two prospective clinical trials comparing the efficacy of high and low glycine containing amino acid solutions.

Glycine has been regarded as a poor source of nitrogen for total parenteral nutrition. Two prospective randomised cross over controlled clinical trials were undertaken to compare the efficacy of high and low glycine containing amino acid solutions in parenterally fed malnourished hypoalbuminaemic patients with gastrointestinal disease. In the first study (n = 9), amino acid solutions in which glycine accounted for 23% and 4% of total nitrogen were compared. No statistically significant difference was found in urea nitrogen/total urinary nitrogen excretion (mean (SEM) 83.4 (1.4) v 81.6 (1.7)%, p = 0.31), nitrogen balance (-1.9 (2.4) v -0.6 (2.0) g/day, p = 0.31) or plasma protein concentrations and blood urea nitrogen. In the second extended study (n = 5), there was no significant difference in net whole body protein synthesis (+1.3 (4.7) v-0.2 (3.7) mg/kg/hour, p = 0.69) or fractional (0.403 (0.070) v 0.480 (0.41)%/hour, p = 0.68) and absolute albumin synthesis rates (6.0 (0.9) v 7.2 (0.06) mg/kg/hour, p = 0.22), on comparing solutions of 25% and 8% glycine nitrogen. In addition, a significantly higher proportion of total urinary nitrogen comprised urea when patients received the low glycine containing amino acid source (81.4 (2.5) v 83.8 (3.2)%, p = 0.04). It is concluded that there are no apparent short term nutritional or metabolic disadvantages to using amino acid solutions that contain up to 25% of nitrogen as glycine in total parenteral nutrition.

Adult

Do patients with moderately impaired gastrointestinal function requiring enteral nutrition need a predigested nitrogen source? A prospective crossover controlled clinical trial.

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease.

Dietary Proteins

Effects of olsalazine and sulphasalazine on jejunal and ileal water and electrolyte absorption in normal human subjects.

The effect of sulphasalazine and olsalazine on jejunal and ileal water and electrolyte absorption was investigated in normal subjects by a steady state intestinal perfusion of a physiological glucose bicarbonate electrolyte solution in the absence and presence of increasing concentrations of each drug. (Olsalazine 0.25 g/l, 1.0 g/l, jejunum; 0.5 g/l, 1.0 g/l, ileum; sulphasalazine 0.25 g/l, 0.5 g/l, 2.0 g/l jejunum; 1.0 g/l, 2.0 g/l, ileum.) In the jejunum olsalazine at 1.0 g/l significantly inhibited water, sodium, chloride, and potassium absorption (p less than 0.05). In the ileum olsalazine at 0.5 and 1 g/l significantly inhibited glucose uptake (p less than 0.04) and water absorption (p less than 0.03). In the jejunum sulphasalazine had a dose related and significant inhibitory effect on water, bicarbonate, and sodium absorption and at 2.0 g/l an inhibitory effect on chloride, potassium (p less than 0.005), and glucose (p less than 0.05) absorption. In the ileum sulphasalazine had no significant effect on water and electrolyte absorption. All inhibitory effects were rapidly reversible. These data show that unexplained diarrhoea in patients with ulcerative colitis treated with olsalazine may occur as a consequence of inhibition of water and electrolyte absorption in the small intestine and that the mechanisms of inhibition of sulphasalazine and olsalazine are different.

Adult

Influence of energy and nitrogen contents of enteral diets on nitrogen balance: a double blind prospective controlled clinical trial.

Results of recent controlled studies show that because of difficulties in administering adequate quantities of enteral diet, positive nitrogen balance is not consistently achieved during enteral feeding. In order to determine whether nitrogen balance can be improved in routine clinical practice by prescribing enteral diets containing higher concentrations of nutrients, 118 patients with normal gastrointestinal function needing enteral nutrition were randomised to receive daily 21 of one of three polymeric diets: Standard diet (1.0 kcal/ml; 6.3 gN/l), Energy Dense diet (1.5 kcal/ml; 7.8 gN/l), and Energy-Nitrogen Dense diet (1.5 kcal/ml; 9.4 gN/l. The three diets, administered by continuous nasogastric infusion, were equally well tolerated. Results were analysed only for patients fed five or more days and who received at least 60% of prescribed enteral diet (n = 42). Positive nitrogen balance was achieved only in the patients receiving the Energy-Nitrogen Dense diet (n = 16; + 1.6 (SE) 0.6 gN/d, compared with the Standard diet (n = 12; -3.8 (1.1) gN/d; p less than 0.001), and the Energy Dense diet (m = 14; -1.9 (0.8) gN/d; p less than 0.005). As the findings of this prospective controlled trial show that positive nitrogen balance was not consistently achieved by administering 21 enteral diet containing up to 15.6 gN, consideration could, therefore, be given to routinely using enteral diets containing up to 9.4 gN/l.

Adolescent

Effect of ileal infusion of glycochenodeoxycholic acid on segmental transit, motility, and flow in the human jejunum and ileum.

The hypothesis that the presence of glycochenodeoxycholic acid (GCDC) in the human Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the been tested in healthy volunteers. Mean transit times, flow rates and intraluminal pressures in a 40 cm jejunal segment proximal (n = 6) and a 40 cm ileal segment distal (n = 6) to a GCDC infusion port were measured. During GCDC infusion (60 mumol/min) jejunal and ileal transit were markedly (p less than 0.05) delayed (31.6 (7.7), mean (SEM) v 14.5 (3.8) min and 37.0 (5.7) v 21.0 (3.5) min, respectively), segment volumes increased (141.1 (30.2) v 59.2 (9.9) ml and 173.2 (26.3) v 83.9 (9.5) ml; p less than 0.05), while flow rates did not change significantly (4.6 (0.6) v 4.5 (0.6) ml/min and 4.8 (0.5) v 4.2 (0.3) ml/min, respectively). Ileal pressures (distal to the GCDC infusion port) decreased (p less than 0.05) promptly (1.0 (0.1) min) after the start of GCDC infusion. Inhibition of jejunal motility was more gradual and reached significance (p less than 0.05) only 30 min after beginning of the infusion. Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the 40 cm ileal segment. These observations suggest the existence of an intestinal control mechanism in healthy man, whereby presence of glycochenodeoxycholic acid in the ileum inhibits motility and delays transit in the jejunum and ileum.

Adult

Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal.

Mouth-to-cecum transit and serum bile acid profile after ingestion of a lactulose-labeled liquid meal (440 kcal) were measured in eight patients with gallstones and a radiologically functioning gallbladder before and three to five months after cholecystectomy and in 15 controls. In the patients mouth-to-cecum transit was longer after the operation, 87.5 +/- 18.5 (mean +/- SEM) min vs 57.5 +/- 9.7 min (P less than 0.05). Mouth-to-cecum transit times before and after the operation were not different from controls (58.0 +/- 6.7 min). Serum bile acid AUCs were similar (P = NS) in patients and controls, while total bile acid and cholylglycine fasting concentrations were higher after cholecystectomy (P less than 0.05 and P less than 0.01 respectively). Cholecystectomy prolongs mouth-to-cecum transit of a liquid meal.

Adult

Effect of jejunal infusion of bile acids on small bowel transit and fasting jejunal motility in man.

The effect of jejunal infusion of glycochenodeoxycholic acid and glycocholic acid on small bowel transit time, fasting jejunal motility and serum bile acid concentrations was investigated in groups of five to six healthy subjects. Glycochenodeoxycholic acid at a concentration of 15 mmol/l (total amount: 5 mmol) and glycocholic acid 15 mmol/l (total amount: 5 mmol), both with lecithin 2.5 mmol/l, delayed (p less than 0.02) small bowel transit when compared with a bile acid free infusion [158.3 (12.5) min v 111.7 (17.6) min and 103.3 (21.8) min v 70.0 (14.9) min], inhibited (p less than 0.01 and p less than 0.05 respectively) the percentage duration of pressure activity of phase 2 [13.1 (1.8)% v 28.1 (3.4)% and 29.2 (5.5)% v 34.9 (3.9)%], but did not change duration of migrating motor complex, or of its phases. Glycochenodeoxycholic acid 10 mmol/l (total amount: 3.3 mmol), either with or without lecithin, did not delay small bowel transit significantly [145.0 (13.2) min v 115.0 (19.5) and 90.0 (11.7) min v 84.0 (8.3)]. When bile acids were infused, serum bile acid curves were similar to those obtained after a liquid meal and the peak serum bile acid concentration occurred 33.7 (6.6) min before (p less than 0.001) completion of small bowel transit. These observations suggest a role for endogenous bile acids in the regulation of small gut motility.

Adult

Inhibition of jejunal water and electrolyte absorption by therapeutic doses of clindamycin in man.

A steady-state perfusion technique has been used in vivo in normal subjects to show that at concentrations occurring during therapeutic use (500 mg/1, 1.1 mmol/l) the antibiotic clindamycin reversibly inhibits bicarbonate-stimulated water and electrolyte absorption from the human jejunum. Lactose-stimulated water and electrolyte absorption was not affected by the addition of clindamycin at the same concentration. Clindamycin-induced malabsorption of water and electrolytes may contribute significantly to the diarrhoea that occurs during clindamycin therapy in the absence of pseudomembranous colitis.

Adolescent

Fulminating necrotizing amebic colitis with perforation: case report and review.

A seriously ill patient with diffuse abdominal tenderness of unknown cause is described. The diagnosis proved to be fulminating necrotizing amebic colitis with perforation. This case report serves as a reminder that amebiasis may occur in patients who have not been outside Canada, that it may readily be confused with other types of inflammatory bowel disease, and that particular care should be taken in obtaining a history of exposure. Before inflammatory bowel disease is diagnosed not only should the usual diagnostic tests such as stool examination and mucosal biopsy be done, but also serologic testing for amebiasis should be carried out.

Adult

Anaphylactic-like reaction to suxamethonium.

A young woman developed an anaphylactic-type reaction during induction of anaesthesia, which was later shown to be due to suxamethonium, to which the patient had not been previously exposed. In vitro testing identified not only suxamethonium as the causative agent, but also other potentially hazardous agents, pharmacologically and chemically related to suxamethonium. Furthermore, 'unrelated' neuromuscular blocking drugs elicited no reaction from the patient's leucocytes, suggesting that in future anaesthesia these agents may be used with little risk. The leucocytes of the patient's parents and brother were also tested, the brother showing a minimal positive reaction. Skin testing confirmed the significance of the in vitro histamine release by the patient's leucocytes.

Adult

The effect of insulin treatment on the metabolic response to glucagon in diabetes.

The metabolic response to intravenous glucagon was studied in insulin requiring diabetes before, 1 week and 1 month after treatment with insulin. The rise in plasma 3-hydroxybutyrate following glucagon in the untreated state was converted to a fall after 1 month on insulin. It is suggested that this response could provide a measure of the biological effectiveness of circulating insulin. There was no change in plasma cyclic AMP response to glucagon after treatment with insulin.

Adult