Biomedical subjects
M F Robinson
Publications and source records attributed to M F Robinson.
Screening for MEN 2 with biochemical and genetic markers.
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Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2.
The hereditary conditions of primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2 (MEN 2) are rare clinical entities. The initial reports of two families in which the two conditions coincided have led to the identification of at least eight additional families with this clinical syndrome. In this report we describe the clinical features in five of these eight families. The salient feature in these five families is the presence of unilateral (46%) or bilateral (64%) pruritic and lichenoid skin lesions located over the upper portion of the back. Family members describe these skin lesions as intermittently intensely pruritic leading to scratching and excoriation of the upper back region. The presence of MEN 2 has been documented in 97% of family members with this skin lesion, the one exception being a child who is at risk for development of MEN 2A in whom the diagnosis has not yet been made. Of family members who have MEN 2A, 27% do not have an identifiable skin lesion, although the skin lesion developed in one patient two years after a curative thyroidectomy for medullary thyroid carcinoma (MTC). Four of the five families have members with pheochromocytoma; one with five affected members has only MTC. The finding of this clinical syndrome in geographically diverse portions of the world and the lack of overlap with MEN 2A without the skin lesion suggest it is a distinct clinical variant of MEN 2A.
Influence of preservation or perfusion of intraoperatively identified spinal cord blood supply on spinal motor evoked potentials and paraplegia after aortic surgery.
Permanent ligation of arteries supplying blood to the spinal cord in operations for aortic aneurysm can lead to spinal cord ischemia, which can result in either paraparesis or paraplegia. This report describes a rapid method of intraoperative identification of those arteries that supply the spinal cord by use of an intrathecal platinum electrode to detect hydrogen in solution that has been injected into the aortic ostia. Preservation or perfusion of those identified arteries supplying the spinal cord may decrease the rate of postoperative neurologic complications. Of 28 porcine experiments with postoperative observation for 24 hours, there were 3 initial pilot experiments in which saline saturated with hydrogen was injected into the temporarily cross-clamped aorta. Twenty animals were then randomized to (1) preservation of only the vessels sequentially identified to supply blood to the spinal cord from T-13 to L-5 (n = 10); (2) division of the vessels supplying the spinal cord (n = 10). A further five animals underwent perfusion experiments wherein the identified cord arteries were perfused by a shunt, the other nonsupply arteries were divided, and the aorta was kept clamped for 45 minutes. Spinal motor evoked potentials were elicited with an intrathecal electrode and were highly sensitive for paralysis. Paralysis occurred in 0/3 pilot (p less than 0.013 vs division); 8/10 division; 1/10 preservation (p less than 0.0017 vs division); and perfusion 1/5 (p less than 0.025 vs division). Results of a pilot study in eight humans shows that the technique can be used to rapidly identify segmental arteries supplying the spinal cord, to determine if distal perfusion is supplying the spinal cord with blood flow, and if reattached segmental arteries are patent.
Selenium distribution in blood fractions of New Zealand women taking organic or inorganic selenium.
Three groups of 11 New Zealand women each received, for 32 wk, yeast tablets with no added selenium (placebo) or 200 micrograms Se/d in tablets either as selenate or as selenium-enriched yeast (SeMet) in a double-blind selenium trial. Plasma and erythrocyte (RBC) samples were collected bimonthly. Gel filtration of plasma from women taking SeMet revealed two major selenium-containing peaks with most of the selenium in the second peak. In contrast, the first peak contained most of the selenium in plasma from women taking selenate. Chromatography of RBC lysates indicated that the majority of the selenium was with hemoglobin (Hb) in women taking SeMet but was about equally distributed between glutathione peroxidase (GSH-Px) and Hb in women taking selenate. The percentage of selenium associated with GSH-Px was found to be greater in RBCs and plasma of women taking selenate than of those taking SeMet.
Selenium content of foods consumed in Otago, New Zealand.
Selenium (Se) concentrations were determined in over 600 foods sampled in Dunedin, New Zealand. Foods included those produced in the region, foods which were expected to contribute significantly to the total Se intake, breads and other wheat products which might be affected by the importation of Australian wheat, and imported vegetarian foods. Foods with the highest Se concentrations were brazil nuts, sunflower seeds and all varieties of fish and kidneys. Somewhat lower concentrations were found in liver, pork, chicken, eggs, cashew nuts, soybeans and mushrooms. Vegetables, fruits, cereals and milk products were generally low in Se with the exceptions of mushrooms, imported legumes, rice and bananas. Those foods showing the greatest difference in Se content from those of other countries were cereal products and meat foods. The effect of a number of cooking methods on Se concentrations indicated that in general, little Se was lost during cooking. The importation of a shipment of high-Se wheat from Australia in 1984 raised Se concentrations in breads and other wheat products two to four fold.
The extent of breast feeding in Dunedin 1974-83.
This study examined breast feeding practices in Dunedin, and aimed to identify determinants of breast feeding in this population. Infants' records were used for a 10 year period (1974-83) from the Royal New Zealand Plunket Society. An upward trend in breast feeding prevalence was observed. Breast feeding was more common in mothers of high socioeconomic status (p less than 0.001), in those who were living with a spouse (p less than 0.001) and when mothers attended parental classes (p less than 0.025). First time mothers tended to breast feed for a shorter time (p less than 0.05). Early introduction of other foods shortened the duration of breast feeding (p less than 0.001). The increase in breast feeding which has occurred in many parts of the western world was also found in Dunedin.
Reduced selenium in asthmatic subjects in New Zealand.
Selenium is an essential component of glutathione peroxidase, an enzyme that helps protect cells against oxidation damage and modulates the lipoxygenase pathway of arachidonic acid metabolism. Low selenium concentrations might therefore influence the inflammatory process in asthma by reducing the activity of glutathione peroxidase. Whole blood and plasma selenium concentrations and glutathione peroxidase activity have been measured in 56 asthmatic patients and 59 non-asthmatic control subjects in New Zealand, a country with a low dietary selenium intake and a high prevalence of asthma. When compared with control subjects the asthmatic patients had lower values for whole blood selenium concentrations (-4.9, 95% confidence interval -10.2 to 0.4 ng/ml) and glutathione peroxidase activity (-3.3, 95% CI -5.8 to -0.8 units/g Hb). There was a 1.9 and 5.8 fold increased risk of asthma in subjects with the lowest range of whole blood selenium concentration and glutathione peroxidase activity respectively (95% CI 0.6 to 5.6 and 1.6 to 21.2). Levels were lower in patients and control subjects without an atopic predisposition, but were not affected by prednisone use. Similar differences between the asthmatic and control subjects were not observed for selenium concentration or glutathione peroxidase activity measured in plasma, which reflects short term rather than long term selenium content. These findings are consistent with the hypothesis that low selenium concentrations may have a role in the pathogenesis of asthma in New Zealand.
Chemiluminescence of peripheral polymorphonuclear leukocytes from adult periodontitis patients.
Polymorphonuclear leukocytes (PMN's) constitute a primary host resistance factor against infection. This study investigated the chemiluminescent (CL) response of peripheral blood PMN's isolated from human subjects with adult periodontitis. 32 subjects were categorized on the basis of age and periodontal disease status into 4 equal groups--young healthy, young diseased, old healthy and old diseased. PMN CL was stimulated using heat-killed, serum-opsonized Fusobacterium nucleatum--a specific periodontopathic gram-negative anaerobe, and Escherichia coli as a gram-negative control organism. The results showed a statistically significant enhancement (p less than 0.05) in the CL response, which was cell associated, in the young diseased subjects. This was not seen in the old subjects (p greater than 0.05), suggesting that in periodontal disease in young subjects the peripheral blood PMNs may be in a metabolically activated state. There was nevertheless a degree of variability between individual subjects within each of the 4 clinical groups.
Selenium in human nutrition in New Zealand.
New Zealand's soil has a low concentration of selenium (Se), and its residents have a lower Se status than do most other peoples. However, New Zealanders do not suffer from the Se-responsive ills that afflict their farm animals and some people in China. New Zealanders, particularly those in the South Island, may have adapted to their low Se environment by thriftiness in urinary excretion of Se. Low glutathione peroxidase activities in their tissues have not resulted in noticeable damage or changes. The enzyme activity can be raised to a plateau by Se supplements, but there is no evidence that supplementation leads to better health. Since patterns of coronary heart disease, hypertension, and cancer in New Zealand resemble those in other Western countries, no direct link between these diseases and Se level is likely.
Inhibitory effect of [Tyr34]bPTH-(7-34)-amide on bPTH-(1-34) ability to reduce uterine contraction.
Synthetic bovine parathyroid hormone containing the 1-34 NH2-terminal amino acids [bPTH-(1-34)] inhibits uterine contraction stimulated by a variety of agonists. Previously, we reported that the parathyroid hormone analogue [Nle8, Nle18, Tyr34]bPTH-(3-34)amide [NTA-(3-34)] antagonized this effect of bPTH-(1-34) while the analogue [Tyr34]bPTH-(7-34)amide [bPTH-(7-34)] used in this study stimulated uterine contraction. However, contrary to this previous report, bPTH-(7-34) in the present study failed to initiate a contractile response and instead resulted in an inhibitory response to the bPTH-(1-34) effect on uterine contraction in a dose-related manner. The inhibitory response of bPTH-(7-34) was further confirmed by demonstrating that this preparation of bPTH-(7-34) was capable of blocking bPTH-(1-34)-stimulated adenylate cyclase activity on particulate fractions of osteoblast-like cells from neonatal mouse calvarial. These results are consistent with those in the literature for the antagonistic effect of the 7-34 PTH fragment.
Unusually high intake and fecal output of cadmium, and fecal output of other trace elements in New Zealand adults consuming dredge oysters.
The concentration of cadmium in the New Zealand dredge oyster Tiostrea lutaria (commonly known as a Bluff oyster) is sufficiently high so that the ingestion of just one oyster can more than double a normal daily dietary intake of cadmium for a New Zealand adult. A survey of 75 adults (18-76 years old) associated with the oyster fishing industry in Bluff, Southland, New Zealand, was carried out before and at the end of the oyster season. Preseason intakes (from dietary history questionnaires and from 3-day fecal collections) of cadmium, selenium, zinc, copper, and manganese were normal for a New Zealand adult not consuming Bluff oysters. The subjects were classified according to their reported average oyster consumption during the 6 months of the oyster fishing season; the subjects who consumed more oysters were more likely to smoke cigarettes. The end-season fecal output of cadmium confirmed the reported average oyster intakes: Category I (0-5 oysters/week): 15 +/- 8 (mean +/- SD) micrograms Cd/day; Category II (6-23 oysters/week): 84 +/- 134 micrograms Cd/day; Category III (24-71 oysters/week): 129 +/- 144 micrograms Cd/day; Category IV (72+ oysters/week): 233 +/- 185 micrograms Cd/day. The fecal output of selenium as well was increased by the consumption of many oysters but the fecal outputs of zinc, copper, and manganese were not. Using fecal cadmium excretion to predict dietary cadmium intake, 8-15% of the subjects in this study were identified as having an intake of cadmium which has been associated with an increased prevalence of tubular proteinuria. The highest individual daily fecal excretion of cadmium at the end of the season was 580 micrograms Cd/day, i.e., a daily excretion equivalent to more than 10 times above the weekly intake provisionally considered tolerable (400-500 micrograms Cd/week; WHO, 1972). Continued investigations on this population group will determine whether there are any health consequences of these extremely high cadmium intakes.
Selenium and vitamin E supplementation: activities of glutathione peroxidase in human tissues.
Twenty-seven New Zealand women received daily for 4 wk, 200 micrograms selenium as sodium selenite, 170 mg alpha-tocopherol acetate, or a placebo. Se supplementation raised platelet selenoglutathione peroxidase (Se-GSHPx, p less than 0.001) and also Se and Se-GSHPx in whole blood and plasma. Se concentrations and Se-GSHPx activities in liver biopsies taken after supplementation were greater (p less than 0.05) for the Se group and a good correlation was found between Se and Se-GSHPx in liver and muscle for all subjects. Platelet Se-GSHPx correlated well with Se and Se-GSHPx in liver, indicating its suitability for assessing Se bioavailability. This is the first reported study of relationships between Se and Se-GSHPx in human liver and muscle tissue and platelet Se-GSHPx after Se supplementation. These observations verify in man relationships observe in animal studies, giving support to assumptions made in methods for assessing Se status and bioavailability in man, in particular the use of platelet GSHPx.
1988 McCollum award lecture. The New Zealand selenium experience.
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Blood selenium and glutathione peroxidase activity of populations in New Zealand, Oregon, and South Dakota.
The relationship of whole blood selenium (Se) to glutathione peroxidase (GPX) activity was examined for individuals in New Zealand, Oregon, and South Dakota who represented, respectively, populations with exposure to low, medium, and high amounts of Se. The mean (respective) blood Se levels were 60, 200, and 400 ng/ml. Intergroup differences in blood Se levels were highly significant (P less than 0.001). GPX assays were performed using two variations of an enzyme-coupled procedure to assess the equivalence of the two methods. Despite a fourfold difference in absolute activities measured by these methods, the GPX activities were highly correlated (r = .86) between procedures. Average blood GPX activity was significantly lower (P less than 0.001) for the New Zealand group compared with the other two groups, but there was no difference in GPX activities between the Oregon and South Dakota groups. Linear regression of GPX vs. Se values within each group indicated a significant correlation of these parameters only in the New Zealand group (r = .46, P less than 0.01). Comparison of these parameters for combined data from all three groups also showed a significant positive correlation (r = .60, P less than 0.001). A saturation model (In GPX = k1 + k2 (Se)-1)) fits the combined data better (r = .80, P less than 0.01) than does direct comparison of the two parameters. These results suggest that GPX activity is an appropriate indicator of human Se status only in populations with below normal exposure to Se, as activity of this enzyme is saturated at relatively low levels.
The absence of adaptive changes in tissue activities of glutathione-S-transferase, superoxide dismutase and catalase following selenium and vitamin E supplementation in subjects with low selenium status.
Three groups of New Zealand women were given daily in a double blind randomised study, 200 micrograms Se as sodium selenite, 170 mg alpha-tocopherol or a placebo for 4 wk. Activities of glutathione-S-transferase, superoxide dismutase and catalase were assayed in erythrocytes, plasma and platelets and in liver and muscle biopsy tissues. No changes in activities of any of these tissue enzymes were observed in any of the three groups. There were also no changes in non-selenium dependent glutathione peroxidase activities in liver or plasma. The lack of changes in any of these enzymes following selenium supplementation suggests that adaptive changes to the low selenium status of these subjects had not occurred through these lipid peroxidation defense mechanisms.
Prevention of gastric mucosal lesions following aortic cross-clamping.
Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).
Altered platelet lipoxygenase activity in patients with low selenium.
1. Arachidonic acid metabolism through the lipoxygenase pathway in platelets was investigated in 11 patients with low selenium (Se) nutritional status and compared with 14 patients with a normal Se status. 2. Plasma and whole blood Se levels, as well as plasma, whole blood and platelet glutathione peroxidase (GSHPx) activity, were measured in both groups and found to be significantly lower in the group with low Se status. 3. Studies on [14C]arachidonic acid stimulated platelets demonstrated that reduced conversion of the active metabolite 12-hydroperoxyeicosatetraenoic acid to 12-hydroxyeicosatetraenoic acid occurred in patients with low Se nutrition. 4. Changes in [14C]arachidonic acid metabolism are attributed to reduced activity of the seleno-enzyme GSHPx. The effects of other factors cannot be entirely excluded.