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Biomedical subjects

J M Wishart

Publications and source records attributed to J M Wishart.

At least 19 recordsLinked to original sources

The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects.

Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a "standard' diet and an identical diet supplemented with 440 g/day of glucose for 4-7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82 +/- 8 vs 106 +/- 10 min, p = 0.004) and fructose (73 +/- 9 vs 106 +/- 9 min, p = 0.001). After ingestion of glucose, plasma concentrations of insulin (p < 0.05) and gastric inhibitory polypeptide (p < 0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p < 0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.

Adult

Effect of age on bone density and bone turnover in men.

OBJECTIVE: Little is known about the pattern of age-related bone loss in men, and although androgens are required for optimum bone mass it is not clear whether the fall in bone mass with age in men is related to falling androgens. DESIGN: Cross-sectional measurement of bone density, at five sites, and markers of bone resorption and formation in 147 normal volunteers aged 20-83 years. SUBJECTS: Healthy laboratory workers, hospital staff, their relatives, and husbands of women attending our osteoporosis clinic. MEASUREMENTS: Forearm density (fat corrected), spine L2-L4, femoral neck, Ward's triangle and trochanter density; serum procollagen I C-terminal extension peptide, osteocalcin, bone alkaline phosphatase and collagen I C-terminal telopeptide; fasting urine hydroxyproline/creatinine, pyridinoline/creatinine and deoxy-pyridinoline/creatinine; and free androgen index (FAI), measured as serum testosterone/sex hormone binding globulin. RESULTS: Bone loss accelerated at most sites after age 50. There was a significant fall in FAI from the third decade onwards. The levels of all bone markers fell with age. CONCLUSIONS: Bone loss in men appears to accelerate from age 50 and is associated with decreased bone formation which may be associated with falling levels of free androgen.

Adult

Relationship between fractional calcium absorption and gastric emptying.

The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.

Acetaminophen

A double blind study of itraconazole vs griseofulvin in patients with tinea pedis and tinea manus.

AIM: To compare the efficacy and safety of itraconazole and griseofulvin in a double-blind parallel study of 20 patients with microscopically and/or culturally proven tinea pedis and/or tinea manus. METHODS: A 4 week study was undertaken with patients randomised to receive either itraconazole 100 mg or griseofulvin 500 mg once daily for 4 weeks. Microscopy and cultures were performed prior to and at the end of the treatment and 2 weeks posttreatment. RESULTS: After 4 weeks therapy, 50% of itraconazole-treated patients and 30% of griseofulvin-treated patients had negative microscopy; 70% and 50% of these patients, respectively, had negative microscopy at follow up 2 weeks later. A combined score of all clinical assessments showed a statistically significant (p < 0.05) difference at the follow up visit in favour of itraconazole. There was no statistically significant difference with regard to haematological or biochemical measurements, or in urinalysis results, either within or between treatment groups. Six patients reported mild adverse effects (itraconazole = 5, griseofulvin = 1), none of which warranted treatment withdrawal. CONCLUSION: The findings of this study suggest that itraconazole is more effective than griseofulvin in the symptomatic treatment of tinea pedis and/or manus.

Adult

Biochemical effects of a calcium supplement in postmenopausal women with primary hyperparathyroidism.

Oral calcium loading is known to decrease parathyroid hormone levels in primary hyperparathyroidism. We have examined the effects of a calcium supplement on bone resorption in postmenopausal primary hyperparathyroidism. Fasting blood and urine samples were obtained in 12 postmenopausal women (median age 64 yr) with primary hyperparathyroidism associated with mild hypercalcemia (plasma calcium < 3.00 mmol/l). Further samples were obtained 12 hours after a 1 g calcium supplement given at 2100 h. After calcium administration there were rises in plasma ionized calcium (p < 0.02), plasma phosphate (p < 0.05) and the renal tubular maximum reabsorption capacity for phosphate (p < 0.01) and falls in parathyroid hormone (p < 0.05) and the renal tubular maximum reabsorption capacity for calcium (p < 0.05). The urinary calcium/creatinine increased (p < 0.01) and the urinary hydroxyproline/creatinine (p < 0.02) fell. These results indicate that calcium loading inhibits bone resorption in postmenopausal women with mild primary hyperparathyroidism.

Absorption

Oral calcium suppresses biochemical markers of bone resorption in normal men.

Calcium supplementation decreases bone resorption and retards bone loss in women. There is little information about the effects of calcium supplementation in men. The effects of a 1-g oral calcium load at 0900 on bone-related biochemical variables were evaluated in 13 normal men (aged 51-70 y). Calcium administration was associated with increases in plasma ionized calcium (P < 0.001) and urinary calcium (P < 0.001), and a decrease in plasma parathyroid hormone (P < 0.001). There was a nonsignificant trend (r = -0.47, P = 0.11) for the decrease in plasma parathyroid hormone to be related to radiocalcium absorption. After the calcium load there were decreases in the urinary hydroxyproline-creatinine ratio from 11 +/- 1.1 to 7.9 +/- 0.6 (P < 0.01), the urinary deoxypyridinoline-creatinine ratio from 14.0 +/- 1.8 to 10.1 +/- 0.9 (P < 0.05), and the urinary pyridinoline-creatinine ratio from 52 +/- 5 to 40 +/- 3 (P < 0.01) between baseline and 6 h. There was no change in plasma osteocalcin. These observations indicate that a 1-g calcium load suppresses biochemical markers of bone resorption for > or = 6 h in normal men and support the concept that calcium supplementation may be useful in the prevention of bone loss in men.

Absorption

Calcitriol (1 alpha,25-dihydroxyvitamin D3) ointment in psoriasis, a safety tolerance and efficacy multicentre study.

30 patients were treated with daily application of calcitriol (1 alpha, 25-dihydroxyvitamin D3) ointment 15 micrograms/g in white petrolatum. The patients were divided into three groups according to the size of their total area of psoriasis. They were treated for 6 weeks, and investigated first with weekly and then with two-weekly estimations of calcium metabolism (serum calcium, 24-hour urinary calcium, parathyroid hormone, 25-hydroxyvitamin D3 and calcitriol). Ninety percent of the patients cleared or improved and there were no significant side effects or local intolerance. Cosmetic acceptance was good. No clinically significant changes in calcium metabolism were observed in spite of calcitriol application ranging between 73.98 and 306.10 micrograms daily (normal daily synthesis being 1-2 micrograms).

Administration, Topical

Primary hyperparathyroidism.

Primary hyperparathyroidism is not rare. It is particularly common after the age of 50 and may affect up to 3% of postmenopausal women. It is commonly found as a result of blood tests performed for other reasons and is therefore often asymptomatic. Surgical treatment is recommended for patients with renal stone disease, plasma calcium above 3 mmol/L and accelerated bone loss (e.g., bone density < 3 standard deviations below the young normal mean). There is considerable debate about whether mild asymptomatic disease should be treated, but if there is rapid bone loss, either surgical or medical therapy with hormones or bisphosphonates is indicated.

Aging

Mometasone versus betamethasone creams: a trial in dermatoses.

AIM: To compare the efficacy and safety of mometasone furoate cream 0.1% applied daily versus betamethasone valerate cream 0.1% applied twice daily in a variety of dermatoses. METHODS: A 4 week study was undertaken of patients with at least moderately severe dermatoses as judged by scoring of a target lesion. Weekly global improvement was assessed, as well as change in target lesion scores. Local side effects were noted including observation of atrophy. RESULTS: Fifty eight patients in three centres completed the study, 30 in the betamethasone group and 28 in the mometasone. There was no difference in demographic variables or disease severity in each group or any difference between the three investigator gradings of initial severity. There was a rapid onset of improvement in both groups by day seven (scores being reduced by 72% in the betamethasone group and 65% in the mometasone group). By the fourth week visit there was 90% reduction in the betamethasone group score and 93% in the mometasone. There was no significant difference between the groups. CONCLUSION: Mometasone furoate cream 0.1% applied daily in dermatoses is as effective as betamethasone valerate 0.1% cream. Both creams had rapid onset of action and had no signs of atrophy. Better patient compliance could be expected with the convenience of mometasone cream being applied daily.

Administration, Cutaneous

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post-menopausal osteoporosis.

OBJECTIVE: Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post-menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post-menopausal osteoporosis. DESIGN/PATIENTS: The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post-menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women. MEASUREMENTS: We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxyproline/creatinine molar ratios. RESULTS: After 4 months of treatment norethisterone produced a fall in plasma calcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P < 0.001), primarily in the non-ionized calcium, due to a decrease in plasma bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). There were decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 to 0.19 +/- 0.02, P < 0.01) and sodium/creatinine (from 15 +/- 1.1 to 10 +/- 0.93, P < 0.001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < 0.001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P < 0.01). Both the urinary hydroxyproline/creatinine (P < 0.001) and plasma alkaline phosphatase (P < 0.001) fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0.81 +/- 0.10 fx/h (P < 0.01). There was no change in serum 1,25-dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P < 0.05) and a decrease in forearm fat content (P < 0.02). After two years treatment with norethisterone fat-corrected forearm bone mineral content rose (mean change 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS: These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.

Adult

The effect of chlorothiazide on bone-related biochemical variables in normal post-menopausal women.

OBJECTIVE: To evaluate the effects of short-term administration of chlorothiazide on fasting urinary hydroxyproline, an index of bone resorption, and other bone-related biochemical parameters in normal post-menopausal women. DESIGN: Subjects served as their own control before and after chlorothiazide treatment. SETTING: Subjects were recruited by advertisement. PARTICIPANTS: Thirteen healthy post-menopausal women with a mean age of 65 years. INTERVENTION: Each subject was given chlorothiazide 500 mg bd po for 7 days. Fasting blood and urine samples were obtained immediately before the commencement of chlorothiazide (day 1) and 2 and 7 days after starting chlorothiazide. RESULTS: Chlorothiazide decreased the urinary calcium/creatinine (mean value day 1, 0.267; day 2, 0.143; day 7, 0.135; P < 0.001) and hydroxyproline/creatinine (day 1, 0.0192; day 2, 0.0145; day 7, 0.0139; P < 0.02) molar ratios. CONCLUSION: Chlorothiazide decreases fasting urinary hydroxyproline, a marker of bone resorption in post-menopausal women. This observation supports a potential role for thiazide diuretics in the prevention of osteoporosis. The observed fall in urinary hydroxyproline is of the same order as that seen after treatment with estrogen or calcium supplements.

Acid-Base Equilibrium

Relationships between metacarpal morphometry, forearm and vertebral bone density and fractures in post-menopausal women.

The relationships between metacarpal morphometric, vertebral and forearm density measurements and the prevalence of vertebral and peripheral fractures were examined in 239 postmenopausal women (median age 63, range 32-84 years). Metacarpal cortical area/total area ratio (CA/TA) was measured with needle calipers, forearm mineral density (FMD) by single photon absorptiometry and vertebral mineral density (VMD) by single energy quantitative computed tomography. Of the 239 subjects 97 had not suffered any fractures, 44 had at least one previous vertebral fracture but no peripheral fractures, 41 had a history of peripheral fracture but no vertebral fracture and 57 had suffered both peripheral and vertebral fractures. There were significant correlations between a single measurement of CA/TA and both FMD (r = 0.65, p < 0.001) and VMD (r = 0.41, p < 0.001). Similar correlations existed between the mean of multiple measurements of CA/TA and both FMD and VMD. CA/TA (p < 0.001), FMD (p < 0.001) and VMD (p < 0.001) were reduced in subjects who had suffered fractures, when compared with the no fracture group. The percentage of cases in each of the four fracture groups (vertebral fracture only, peripheral fracture only, peripheral and vertebral fracture, peripheral or vertebral fracture) misclassified with reference to the no fracture group were similar with CA/TA, FMD or VMD measurements. We suggest that metacarpal morphometry, which is widely available at relatively low cost, yields cross-sectional information about bone density and fracture risk, comparable with that obtained by forearm and vertebral densitometry.

Absorptiometry, Photon

Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects.

The effects of erythromycin on gastric emptying and intragastric distribution of a mixed solid/liquid meal, alcohol absorption and small intestinal transit were examined in eight male volunteers. Each subject received, in double-blind randomized order, either erythromycin as the lactobionate (3 mg.kg-1 i.v. over 20 min) or saline immediately before the consumption of a radioisotopically labeled test meal, which consisted of 330 g minced beef and 400 ml of orange juice containing ethanol (0.5 g.kg-1 body weight) and 10 g lactulose. Erythromycin increased the rate of total stomach emptying and proximal stomach emptying of both the solid and liquid components of the meal (p < 0.001), but slowed small intestinal transit (p < 0.01). Peak blood alcohol concentrations (p < 0.01) were higher after erythromycin, with a mean increase of 40%. There was a significant inverse relationship between peak blood alcohol concentrations and the 50% emptying time for the liquid component of the meal after saline (r = -0.70, p < 0.05), but not after erythromycin (r = -0.57, p < 0.1). The total area under the venous blood alcohol concentration time curve (i.e., total absorption) was greater (p < 0.01) after erythromycin. These results suggest that: faster emptying from the proximal stomach contributes to more rapid gastric emptying induced by erythromycin, erythromycin retards small intestinal transit and that erythromycin increases the total amount of alcohol absorbed as well as the rate of alcohol absorption. These latter effects are likely to reflect more rapid delivery of alcohol to the small intestine and reduced metabolism of alcohol by the gastric mucosa.

Adult

Osteoporosis and Klinefelter's syndrome.

OBJECTIVE: We wanted to measure forearm mineral density and bone-related biochemical variables in patients with Klinefelter's syndrome. DESIGN: Measurements made in patients with Klinefelter's syndrome were compared to those obtained in age-matched normal male volunteers. PATIENTS: We studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects. MEASUREMENTS: We measured forearm mineral density, forearm fat content, fat-corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio. RESULTS: Forearm mineral density was lower in the Klinefelter's group than in the control subjects (P less than 0.05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P less than 0.002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P less than 0.002). Serum dehydroepiandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r = 0.64, P less than 0.001), but not in the controls (r = 0.22, NS). Forearm mineral density and fat-corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r less than 0.63; P less than 0.01), but not in the control subjects (r less than 0.03, NS). CONCLUSIONS: Decreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased bone resorption.

Adult

Cigarette smoking and rate of gastric emptying: effect on alcohol absorption.

OBJECTIVE: To examine the effects of cigarette smoking on alcohol absorption and gastric emptying. DESIGN: Randomised crossover study. SETTING: Research project in departments of medicine and nuclear medicine. SUBJECTS: Eight healthy volunteers aged 19-43 who regularly smoked 20-35 cigarettes a day and drank small amounts of alcohol on social occasions. INTERVENTIONS: Subjects drank 400 ml of a radiolabelled nutrient test meal containing alcohol (0.5 g/kg), then had their rates of gastric emptying measured. Test were carried out (a) with the subjects smoking four cigarettes an hour and (b) with the subjects not smoking, having abstained for seven days or more. The order of the tests was randomised and the tests were conducted two weeks apart. MAIN OUTCOME MEASURES: Peak blood alcohol concentrations, absorption of alcohol at 30 minutes, amount of test meal emptied from the stomach at 30 minutes, and times taken for 50% of the meal to leave the proximal stomach and total stomach. RESULTS: Smoking was associated with reductions in (a) peak blood alcohol concentrations (median values in non-smoking versus smoking periods 13.5 (range 8.7-22.6) mmol/l v 11.1 (4.3-13.5) mmol/l), (b) area under the blood alcohol concentration-time curve at 30 minutes (264 x 10(3) (0-509 x 10(3)) mmol/l/min v 140 x 10(3)) (0-217 x 10(3) mmol/l/min), and (c) amount of test meal emptied from the stomach at 30 minutes (39% (5-86%) v 23% (0-35%)). In addition, smoking slowed both the 50% gastric emptying time (37 (9-83) minutes v 56 (40-280) minutes) and the intragastric distribution of the meal. There was a close correlation between the amount of test meal emptied from the stomach at 30 minutes and the area under the blood alcohol concentration-time curve at 30 minutes (r = 0.91; p less than 0.0001). CONCLUSION: Cigarette smoking slows gastric emptying and as a consequence delays alcohol absorption.

Adult