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Biomedical subjects

M F Robinson

Publications and source records attributed to M F Robinson.

At least 73 records · Page 4Linked to original sources

Failure of cimetidine to affect calcium homeostasis in familial primary hyperparathyroidism (multiple endocrine neoplasia, type 1).

Recent reports that cimetidine, a blocker of histamine H2 receptors, lowered serum calcium and/or immunoreactive parathyroid hormone (PTH) concentrations in primary or secondary hyperparathyroidism prompted us to administer the drug (300 mg, orally, every 6 h) to two patients with hyperparathyroidism accompanying familial multiple endocrine neoplasia type 1. The patients were hypercalcemic (10.9--11.2 mg/dl), hypophosphatemic (2.0--2.4 mg/dl), and hypercalciuric (greater than or equal to 410 mg/24 h), with elevated urinary cAMP and phosphate clearance and inappropriately high serum immunoreactive PTH levels. Multiple observations of these variables over 5 weeks of cimetidine treatment showed no systematic changes; in particular, serum and urinary calcium did not change, and there was no evidence of a decreased PTH effect on the kidneys. The data offer no support for the treatment of familial hyperparathyroidism with cimetidine.

Adolescent↗

Relation between erythrocyte selenium concentrations and glutathione peroxidase (EC 1.11.1.9) activities of New Zealand residents and visitors to New Zealand.

1. Erythrocyte, plasma and whole blood selenium concentrations and glutathione peroxidase (EC 1.11.1.9; GSHPx) activities were measured (1) in 104 healthy New Zealand residents living in Otago, a low-soil-Se area (2) in sixty-four surgical patients, including nineteen patients on total parenteral nutrition and twenty-three cancer patients (3) in fifty-two 'overseas subjects' (twenty-five visitors to Otago from outside New Zealand and twenty-seven Otago residents on return from overseas travel). 2. Blood Se concentrations reflected dietary Se intake; means for Otago patients, healthy subjects and overseas subjects were different 0.043, 0.059, 0.136 micrograms Se/ml blood respectively) and mean for overseas residents was greater than for New Zealand overseas travellers. 3. Erythrocyte Se concentration was always greater than plasma Se, and plasma Se was a smaller proportion of erythrocyte Se for patients compared with the controls. 4. GSHPx activities were different in the three groups, and varied directly with erythrocyte Se until a plateau was reached at approximately 0.14 micrograms Se/ml erythrocytes. 5. Overseas subjects showed no relationship between erythrocyte Se and GSHPx activity. This agrees with some overseas studies and the significance of this finding is discussed. 6. Plasma Se concentration remained the most sensitivie index of short-term changes in Se status, and erythrocyte Se and GSHPx activities for long-term changes in New Zealand subjects. Use of these measurements for overseas subjects with higher blood levels is discussed.

Erythrocytes↗

Zinc retention and losses of zinc in sweat by preadolescent girls.

Preadolescent girls, ages 7 to 9 years, were fed levels of zinc ranging from 5.61 to 14.61 mg/day during an 18-day metabolic study. All other nutrients were provided at or above Recommended Dietary Allowance levels. The sweat loss of zinc was measured using an arm-bag method and whole body zinc loss was calculated from whole body nitrogen and arm loss of nitrogen and zinc. Fecal zinc reflected dietary zinc, but urinary zinc remained relatively stable. The mean daily loss of zinc through sweat was calculated to be 1.43 mg. Zinc retentions were not significantly different (P greater than 0.05) though the retention increased generally with intake of zinc. A comparison of these data with previously reported studies indicated that the absorption of zinc was usually in the range of 20 to 30%. Based on sweat losses reported by others and found in this study and on usual absorption of zinc, it appears that diets should provide a minimum of 7 mg of zinc daily for growing children.

Child↗

Blood selenium and glutathione peroxidase activity in normal subjects and in surgical patients with and without cancer in New Zealand.

This study was carried out in Otago, South Island, where most arable land has a low soil selenium content (less than 0.5 microgram/g) and where selenium (Se) responsive diseases in livestock are common. Se concentration in whole blood, erythrocytes and plasma, and activity of glutathione peroxidase (EC 1.11.1.9) were measured in blood from 104 healthy Otago residents, 80 patients with cancer and 66 noncancer surgical patients. The older residents over 60 years had lower blood Se levels (0.047 +/- 0.010 microgram Se/ml blood) than the young and middle-aged (0.060 +/- 0.012 microgram Se/ml). Blood Se levels of cancer patients were no lower than those of elderly subjects and patients without cancer, and were less than half comparable United States values. Blood Se levels were decreasing in two cancer patients, and the lowest values (less than 0.03 microgram Se/ml blood) were obtained for five cancer patients, and two noncancer patients after a long period of inanition; these were similar to values for patients on parenteral nutrition with negligible intakes. Lower blood Se levels were associated with lower serum albumin and enzyme activities. It is suggested that low Se status of cancer patients was more likely a consequence of their illness than the cause of the cancer.

Adult↗

On supplementing the selenium intake of New Zealanders. 1. Short experiments with large doses of selenite or selenomethionine.

1. Urinary and faecal excretion of single oral doses of 1 mg selenium or 0.1 mg Se as selenomethionine (Semet-Se) in solution were studied in two women. Most of the Se was absorbed and little was eliminated in the urine (0.05-0.22 dose). 2. The results have been compared with those from an earlier study (Thomson, 1974) on the same two women after similarly sized doses of sodium selenite (selenite-Se) in solution. Although selenite-Se was almost as well absorbed as Semet-Se more was excreted in the urine (0.41-0.85 dose). 3. Repeated dosing with 1 mg selenite-Se on five consecutive days in one of the women indicated that 1.1 mg had been retained. 4. Twenty patients with muscular complaints from Tapanui (South Otago, New Zealand), a low-Se soil area, ingested 0.5 mg selenite-Se daily for 20 d. Blood Se increased rapidly to almost twice the initial concentration but reached a plateau well below most values reported for residents outside New Zealand. No difference in blood Se concentration was found between those who did or did not report improvement. 5. Spasmodic medication with selenite-Se by some residents near Lincoln (Christchurch, New Zealand) for periods of up to 10 years or more had increased the blood Se somewhat.

Adult↗

On supplementing the selenium intake of New Zealanders. 2. Prolonged metabolic experiments with daily supplements of selenomethionine, selenite and fish.

1. The daily intake of selenium by three subjects was supplemented with 100 microgram Se as selenomethionine (Semet-Se) or sodium selenite (selenite-Se)/d for 10-11 weeks, or with 65 microgram Se as in mackerel (Scomber japonicus) (fish-Se)/d for 4 weeks. 2. Urinary and faecal excretion of Se was measured and also Se concentration in whole blood, plasma and erythrocytes. Measurements on blood were made at intervals after supplementation had ceased. 3. Selenite-Se was not as well absorbed (0.46 of the intake) during the first 4 weeks as Semet-Se (0.75 of the intake) and fish Se (0.66 of the intake). 4. Blood Se increased steadily with Semet-Se, from 0.08 to 0.18 microgram Se/ml, but more slowly with selenite-Se, reaching a plateau in 7-8 weeks at 0.11 microgram Se/ml. Plasma Se increased more rapidly with Semet-Se than with selenite-Se, so that initially with Semet-Se plasma Se was greater than erythrocyte Se. 5. Daily urinary excretion increased with all forms of supplement, with initially a greater proportion of absorbed selenite-Se being excreted than Semet-Se or fish-Se. A close relationship was found between plasma Se and 24 h urinary excretion. The findings suggested that there was a rapid initial excretion of presumably unbound Se then a slower excretion of residual unbound, loosely bound or bound Se. 6. Total retentions of 3.5 mg selenite-Se and 4.5 mg Semet-Se were large when compared with an estimate of body content of 6 mg Se, derived in another paper (Stewart, Griffiths, Thomson & Robinson, 1978). Retention of Semet-Se and fish-Se appeared to be reflected in blood Se, whereas for selenite-Se, blood Se reflected retention for only a short period after which Se appeared to be retained without altering the blood Se. This suggested that Semet-Se and selenite-Se were metabolized differently. 7. A double blind-dosing trail with 100 microgram Semet-Se was carried out for 12 weeks on twenty-four patients with muscular complaints in Tapanui, a low-Se-soil area. Blood Se increased in the experimental group (from 0.067 to 0.143 microgrm Se/ml); clinical findings were not conclusive and will be presented elsewhere. 8. Bood Se was measured in New Zealand residents before travelling to Europe or to North America. On return their blood Se was increased, and depending upon the period of time spent outside New Zealand some values reached concentrations found in visitors and new settlers to New Zealand. 9. The results from these studies and the earlier studies of single and multiple dosing have been used to look at the various criteria in use for assessing Se status of subjects. It is suggested that plasma Se be used in preference to 24 h urinary excretion, and in addition to whole blood Se and glutathione peroxidase (EC 1.11.1.9) activity.

Adolescent↗

Copper, manganese, zinc, nickel, cadmium and lead in human foetal tissues.

1. Concentrations of copper, manganese, zinc, nickel, cadmium and lead were measured in samples of liver, kidney, brain, heart, lung, skeletal muscle and vertebral bone from forty foetuses of 23-43 weeks gestation. 2. Cu concentrations in the liver were up to 100 times those in other tissues, but only those in the brain showed a significant increase with gestational age. 3. Mn concentrations were similar in all tissues; the over-all range was 0.35-9.27 microgram/g dry matter (DM). 4. Concentrations of Zn in the liver were much higher than in other tissues and decreased with gestational age, whereas levels in skeletal muscle increased. 5. In all tissues Ni concentrations were within the range 0.04-2.8 microgram/g DM and levels in kidney and muscle decreased significantly with age. 6. Cd was detected in most of the tissue samples and concentrations were within the range 0.01-0.58 microgram/g DM. 7. Concentrations of Pb, where it was detected, varied from 0.1 to 2.4 microgram/g DM in the soft tissues and from 0.4 to 4.3 microgram/g DM in the bone samples.

Cadmium↗

Quantitative selenium metabolism in normal New Zealand women.

1. Quantitative selenium metabolism has been studied in normal young New Zealand women by measuring total Se intake and urinary and faecal Se output, and by using values for absorption, excretion and turnover of 75Se determined after administration of[75Se]selenomethionine or [75Se]selenite. 2. In a period of 14 d when a normal ad lib. diet was being consumed, mean dietary Se for four women was 24.2 microgram/d, mean urinary Se was 13.1 microgram/d and mean faecal Se was 10.8 microgram/d; mean Se balance during this time was + 0.3 microgram/d. 3. Intestinal absorption of food Se was 0.76--0.83 of intake (mean 0.79). 4. Whole-body Se was calculated in three different ways; (a) using the specific activity of urinary Se and retained whole-body 75Se; (b) using plasma Se and the occupancy of 75Se in whole-body and plasma; (c) using absorbed food Se and the occupancy of absorbed 75Se in whole-body. 5. Whole-body Se calculated from measurements obtained following the administration of [75Se]selenomethionine was 4.7--10.0 mg (mean 6.9) using method (a), 4.1--7.2 mg (mean 5.2) using method (b) and 4.3--8.9 mg (mean 6.2) using method (c). 6. Whole-body Se calculated from results obtained after giving [75Se]selenite was 2.7--3.4 mg (mean 2.9) using method (a), 2.3--5.0 mg (mean 3.5) using method (b) and 2.1--3.0 mg (mean 2.6) using method (c). 7. The results of this study indicate that the minimum dietary requirement of Se for the maintenance of normal human health is probably not more than 20 microgram/d.

Adult↗

Selenium concentration and glutathione peroxidase activity in blood of New Zealand infants and children.

The blood selenium (Se) concentrations of New Zealand children were lower than those reported for children living in other countries. This low blood Se was primarily determined by the low dietary intake of the children which, in turn, reflects the low Se content of New Zealand soils. Blood Se also varied geographically, with age, and with differences in quantities and types of food eaten. Children with phenylketonuria and maple syrup urine disease on synthetic diets had low Se intakes and blood Se concentrations compared with children on normal diets, and blood Se was seen to decrease with the length of time on these diets. A strong correlation (r = 0.62, P less than 0.001) was found between the blood Se levels and glutathione peroxidase activities for 107 children. Glutathione peroxidase activities of the children were lower than activities observed in New Zealand adults, refelecting their lower blood Se concentrations.

Adolescent↗

Selenium concentrations and glutathione peroxidase activities in whole blood of New Zealand residents.

1. A relationship was found between selenium concentrations and glutathione peroxidase (EC 1.11.1.9) activities in whole blood of 264 New Zealand residents (r 0-71, P less than 0-001). 2. New Zealand residents returning from visits overseas of 7 months to 3 years had elevated blood Se, but normal GSH-Px activities, whereas for some new settlers in New Zealand both Se and GSH-Px activities were high.

Adolescent↗

Metabolic studies in rats of 75Se incorporated in vivo into fish muscle.

1. [75Se]selenite of [75Se]selenomethionine was injected in to the coelomic cavity of fish. After 2 d or 14 d the muscle portion of the fish was removed and homogenized. The long-term fate in rats of an oral dose of each labelled homogenate was compared with that of an oral dose of [75Ee]selenite or [75Se]selenomethionine mixed with unlabelled fish homogenate. 2. Urinary and faecal radioactivity were measured during the 1st week and whole-body radioactivity was determined for 10 weeks. Rats were killed at weekly intervals for 4 weeks for analysis of tissue distribution of 75Se. 3. Intestinal absorption of 75Se given as labelled fish homogenate was less complete than that of 75Se mixed with unlabelled homogenate, and the absorption of 75Se from the 14 d-labelled fish homogenate derived from [75Se]selenite was less complete than that of 75Se from the other labelled homogenates. 4. Urinary excretion of absorbed 75Se in the first 7 d was in the range 5--8% absorbed dose and was slightly greater in the rats given 75Se as selenite or derived from selenite than in those given 75Se as selenomethionine or derived from selenomethionine. Endogenous faecal excretion of absorbed Se was similar in all groups, as also were tissue distribution of retained 75Se and long-term whole-body turnover rate. 5. The results of these studies are compared with those of earlier studies of the metabolism in rats of [75Se]selenomethionine, [75Se]selenite, [75Se]selenocystine and 75Se incorporated in vivo into rabbit kidney. There were differences in the initial utilization of 75Se from these various sources but after the 1st week 75Se from all sources appeared to be metabolized similarly, suggesting that for rats dietary Se of all forms is ultimately incorporated into the same metabolic pool.

Animal Nutritional Physiological Phenomena↗

Daily intakes of manganese, copper, zinc and cadmium by New Zealand women.

1. A total of 179 duplicate diets were collected by twenty-three women consuming their habitual diet. Twelve of the subjects were living in a residential hall for students, the others were living in their own homes or in flats. Collection periods varied from 3 to 21 d. 2. Average daily intakes were: manganese 2-7 mg; copper 1-5 mg for diets not containing liver, 7-6 mg for fifteen diets containing liver; zinc 10-0 mg; cadmium 21 microgram for diets not containing liver, 27 microgram for fifteen diets containing liver. 3. The intakes were compared with values for adults from other countries and with current recommended dietary allowances or estimated minimum requirements. Mn intakes were typical for non-vegeratian Western diets. Cu and Zn intakes may have been marginally low. The intakes of Cd were low. 4. Daily intakes of protein (71 g), fat (83 g), fat (83 g), carbohydrate (224 g) and energy (8-1 MJ) from 129 of the diets were similar to recent values obtained for New Zealand women. 5. Subjects living in the residential hall had higher intakes of all nutrients than subjects living in their own homes or flats.

Adult↗

Co-trimoxazole in chronic renal failure--a controlled experiment in Wistar rats.

Co-trimoxazole failed to cause a deterioration in renal function, as measured by pre- and posttreatment plasma urea levels, in groups of Wistar rats with either normal renal function or surgically induced chronic renal failure. In addition tubular necrosis was not produced. Co-trimoxazole does not appear to be extremely toxic to the Wistar rat kidney.

Animals↗