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Biomedical subjects

M F Robinson

Publications and source records attributed to M F Robinson.

At least 19 recordsLinked to original sources
PubMed1997

Long-term supplementation with selenate and selenomethionine: urinary excretion by New Zealand women.

Thirty-six New Zealand women aged between 18 and 23 years received daily for 32 weeks, 200 micrograms Se as Se-enriched yeast (selenomethionine, SeMet), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Mean daily Se excretion increased with both supplements; the selenate group excreted more than the SeMet group, 123 v. 66 micrograms/d respectively at week 2, equivalent to 57 v. 27% of the dose. Thereafter Se output increased for the SeMet group reaching a plateau at about 100 micrograms/d at week 16, when plasma Se had also plateaued at 190 ng/ml. The selenate group had reached an earlier plateau of 110 ng Se/ml at week 7. There was a close relationship between 24 h urine and plasma Se for the SeMet group but not for the selenate group. Renal plasma clearances showed two distinctly different responses; the clearance of 0.4 ml/min reached by the SeMet group at week 2 plateaued as plasma Se increased almost 2-fold; whereas for the selenate group the clearance varied between 0.8 and 1.1 ml/min whilst plasma Se remained almost constant at 110 ng/ml. Previous studies, also of 200 micrograms Se/d as Se-rich bread, in New Zealand (NZ) and elsewhere showed similar responses to Se-yeast; the selenite response was intermediate between selenate and Se-yeast (SeMet). The full significance of these studies awaits identification of Se components in plasma, glomerular filtrate and urine; meanwhile renal clearances serve as a pointer to changes in the distribution of Se-containing fractions in the plasma. Trimethylselenonium was detected in basal urines, and was a minor component in urines of supplemented NZ subjects at about 1% of the total Se.

Adolescent↗
PubMed1996

The changing selenium status of New Zealand residents.

OBJECTIVE: The aim of this paper was to compile all the studies of selenium status carried out in Otago and in other areas of New Zealand in order to follow the history of selenium status in New Zealand residents over the last 20 years. DESIGN: Since 1970 baseline blood samples have been collected from several groups of healthy adult subjects, either for the assessment of Se status or to determine baseline Se levels as part of a number of other studies. A comparison has been made of selenium concentrations recorded in recent published and unpublished studies with earlier studies by the Otago research group, and also those by other groups in New Zealand. SETTING: Otago and other New Zealand centres. RESULTS: Blood selenium concentrations of Otago residents were consistently low from 1972 until 1988 at around 0.77 mumol/l, apart from a temporary increase in 1985, and then rose to reach 1.03 mumol/l in 1991 and 1.19 mumol/l in 1992-3. Blood selenium status reflected changes in the importation of Australian wheat. Correlations between selenium and glutathione peroxidase in whole blood and plasma were consistently high prior to 1989, but were no longer significant from 1990. CONCLUSIONS: The lack of a correlation between selenium and glutathione peroxidase in bloods collected after 1990 indicates that at least for glutathione peroxidase, the selenium intake of New Zealanders is now close to that required for saturation. Whether this is sufficient to meet the requirements for other functional selenoproteins or for a possible cancer prevention effect remains to be determined.

Adult↗
PubMed1995

Antifolates can potentiate topoisomerase II inhibitors in vitro and in vivo.

Antifolates have been shown to increase the DNA strand breaks produced by the topoisomerase inhibitor etoposide. PT523 is a potent new antifolate that cannot be polyglutamated. Human SCC-25 squamous carcinoma cells were exposed to methotrexate, trimetrexate or PT523 at a concentration of 5 microM for 24 h along with various concentrations of etoposide or novobiocin during the final 2 h. Isobologram analysis of the treatment combinations indicated that exposure of the cells to PT523/etoposide, methotrexate/etoposide, PT523/novobiocin, methotrexate/novobiocin and trimetrexate/novobiocin resulted in greater than additive cytotoxicity. DNA alkaline elution studies with the same drug combinations indicated that there were three- to four-fold increases in the radiation equivalent (rad equivalent) strand breaks in the cellular DNA with etoposide or novobiocin along with the antifolate compared with the topoisomerase II inhibitors alone. Tumor growth delay studies were carried out in the murine SCC VII squamous carcinoma. PT523 (0.5 mg/kg) and methotrexate (2 mg/kg) were administered by 7-day continuous infusion while trimetrexate (3.75 mg/kg) was administered intraperitoneally daily on days 7-9. Etoposide (10 mg/kg) and novobiocin (100 mg/kg) were administered intraperitoneally on alternate days (7, 9, 11). The combinations of PT523 with etoposide or novobiocin were significantly more effective than methotrexate and etoposide or novobiocin, producing tumor growth delays of 8.4 days and 6.9 days, respectively. Overall, the antifolate/topoisomerase II inhibitor treatment combinations produced tumor growth delays that were apparently additive to greater than additive.

Animals↗
PubMed1995

Restoration of tumor oxygenation after cytotoxic therapy by a perflubron emulsion/carbogen breathing.

Female, Fisher 344 rats bearing 13762 mammary carcinoma implanted subcutaneously in a hind limb were treated with standard therapeutic single doses of antitumor treatments of several types including: 1) antitumor alkylating agents (cisplatin, cyclophosphamide); 2) natural products (adriamycin, taxol and etoposide); 3) antimetabolites (5-flourouracil); 4) hypoxic cell selective agents (mitomycin C, SR-4233) as well as 5) fractionated radiation therapy (3 Gray daily for 5 days). The oxygen levels in the tumors were measured in the absence of treatment and 24 hrs. after treatment using an Eppendorf p02 histograph. Fifty- to sixty-points were measured per tumor and 8-10 tumors comprised each group. The tumors were more hypoxic post treatment with every anticancer drug or radiation. The percent of p02 readings < or = 5 mmHg in the untreated tumors ranged from 85% (x-rays) to 59% (etoposide). Administration of the perflubron emulsion (8 ml/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the tumors such that the percent of pO2 readings < or = 5 mmHg was 32% in the untreated controls and ranged from 27% (x-rays) to 56% (adria) in the treated tumors. These results indicate that administration of a perflubron emulsion/carbogen can increase the oxygen content of tumors when hypoxia is the result of cytotoxic therapy.

Animals↗
PubMed1995

Increased tumor oxygenation and radiation sensitivity in two rat tumors by a hemoglobin-based, oxygen-carrying preparation.

The rat 13762 mammary carcinoma and the rat 9L gliosarcoma were grown subcutaneously in a hind limb of female, Fisher 344 rats. The oxygen content of the tumors was determined using an Eppendorf pO2 histograph. Fifty-to-sixty oxygen measurements were made per tumor and there were 8-to-10 animals per group. The percent of pO2 readings < or = 5 mmHg in the mammary carcinoma was 49%, this was decreased to 34% by administration of the hemoglobin preparation (8 ml/kg) and further decreased to 29% when carbogen (95% O2/5% CO2) breathing was added to administration of the hemoglobin preparation. The percent of pO2 readings < or = 5 mmHg in the gliosarcoma was 49%, this was decreased to 24% by administration of the hemoglobin preparation and further decreased to 0% when carbogen breathing was added to administration of the hemoglobin preparation. Therapeutic response was assessed over a single-dose range of radiation therapy (10, 20 and 30 Gray). The dose modifying factor produced by the hemoglobin preparation/air was 1.6 and by the hemoglobin preparation/carbogen was 2.7 in the rat 13762 mammary carcinoma. The dose modifying factor produced by the hemoglobin preparation/air was 1.9 and by the hemoglobin preparation/carbogen was 2.9 in the rat 9L gliosarcoma. Administration of a hemoglobin-based oxygen carrier reduced tumor hypoxia and increased tumor response to radiation therapy.

Adenocarcinoma↗
PubMed1995

Antiangiogenic treatment (TNP-470/minocycline) increases tissue levels of anticancer drugs in mice bearing Lewis lung carcinoma.

Although the antiangiogenic agent TNP-470 does not, in general, increase the cytotoxicity of anti-cancer therapies in cell culture, the antiangiogenic agents TNP-470 and minocycline individually and especially in combination have been shown to increase the tumor growth delay produced by several standard cytotoxic therapies in the Lewis lung carcinoma. In an effort to understand the mechanism by which the antiangiogenic agent combination TNP-470/minocycline potentiates the antitumor activity of cytotoxic therapeutic agents in vivo, the biodistribution of [14C]-cyclophosphamide and cis-diamminedichloroplatinum(II) was determined 6 h after cytotoxic drug administration in animals bearing Lewis lung carcinoma pretreated with TNP-470/minocycline and in animals without pretreatment. Higher levels of 14C and platinum were found in 9 tissues (including tumor) except blood in animals pretreated with TNP-470/minocycline. The increased drug levels in the tumors may be sufficient to account for the increased tumor growth delays observed previously. DNA alkaline elution of tumors from animals pretreated with TNP-470/minocycline showed increased DNA cross-linking by both cyclophosphamide and cis-diamminedichloroplatinum(II). The possible implications of these results are discussed.

Animals↗
PubMed1993

Nutrient intake of Dunedin women during pregnancy.

AIM: To assess the adequacy of dietary intake of women during the three trimesters of pregnancy. METHOD: Dietary intakes of 63 primiparous and 32 multiparous healthy pregnant Dunedin women were obtained by 3 day weighed records at about 12 weeks, 24 weeks, and 36 weeks of gestation. Energy and nutrient intakes were derived using the University of Otago food composition database. RESULTS: Mean energy and nutrient intakes differed remarkably little between primiparous and multiparous women; data were combined for analysis. Energy intakes at first and second trimesters were similar to that for non pregnant women in the National Heart Foundation 1977 survey but greater than in the LINZ 1989 survey. Energy and carbohydrate intakes had increased at third trimester; across the trimesters carbohydrate accounted for 44-46% energy intake, fat for 39% and protein for 15%. Protein intakes at the 10th centile were almost the same as the recommended low risk intake of 51 g/d set by WHO/FAO: No vitamin or mineral showed a trend in intake through the trimesters. Vitamin and mineral intakes were in general greater for the pregnant women than for nonpregnant women in both 1977 and 1989 studies. By comparison with recommended intakes for NZ, Australia, USA and UK, intakes for folate, vitamin B-6, iron and possibly zinc and thiamin were potentially inadequate. Over 10% were heavy smokers and 20% were light smokers; nutrient intakes were less for the smokers than for the nonsmokers, as were birth weights; energy intakes for smokers had not increased at the third trimester. CONCLUSION: An improvement in quality of diet is needed during pregnancy and in prenatal period; smoking should continue to be strongly discouraged.

Adult↗
PubMed1993

Oxygenation of tumors by a hemoglobin solution.

Tumor oxygen tensions were measured using a computer-controlled PO2 microelectrode in two preclinical solid tumor models, the rat 9L gliosarcoma and the rat 13672 mammary carcinoma. Tumor oxygenation profiles were determined under four conditions: (a) during normal air breathing, (b) during carbogen breathing, (c) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with normal air breathing and (d) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with carbogen breathing. Both tumors had severely hypoxic regions under normal air-breathing conditions. Although carbogen breathing increased the oxygenation of the better-oxygenated portions of the tumor, it made no impact on the severely hypoxic tumor regions. Administration of the hemoglobin solution was effective in increasing the oxygenation throughout both tumors under normal air-breathing conditions. The addition of carbogen breathing to administration of the hemoglobin solution eliminated severe hypoxia in the 9L gliosarcoma and markedly reduced the severely hypoxic regions of the 13672 mammary carcinoma. At 24 h after administration of the hemoglobin solution the 13672 mammary carcinoma showed greater hypoxia than before treatment, which was partially corrected with carbogen breathing.

Adenocarcinoma↗
PubMed1993

Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women.

Thirty-three New Zealand women aged 18-23 years received daily for 32 weeks, 200 micrograms Se as Se-enriched yeast (selenomethionine), or brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind trial. Se supplementation raised (P = 0.001) platelet glutathione peroxidase (EC 1.11.1.9; GSHPx) activity, and also Se and GSHPx in whole blood, erythrocytes and plasma. Selenomethionine was more effective in raising blood Se concentrations than selenate, but both were equally effective in raising GSHPx activities in whole blood, erythrocytes and plasma, indicating a similar bioavailability for the two forms. These observations and those of gel filtration studies of erythrocytes and plasma proteins reported elsewhere (Butler et al. 1991) are consistent with the incorporation of Se from selenomethionine into a general tissue protein pool while selenate is directly available for GSHPx synthesis, and explain the poorer correlation between Se and GSHPx in individuals with higher Se status. However, selenate raised platelet GSHPx activities to a greater extent than did selenomethionine suggesting some other effect of selenate on platelets which needs further investigation. A response of GSHPx activity in these New Zealand subjects indicates that their dietary Se intake is insufficient to meet recommended intakes based on the criterion of saturation of GSHPx activity, and could reflect a marginal Se status. The level of blood Se necessary for saturation of GSHPx of about 100 ng Se/ml whole blood confirms observations in earlier studies.

Adolescent↗
PubMed1992

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.

Adolescent↗
PubMed1991

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.

Aged↗
PubMed1991

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.

Adult↗
PubMed1990

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.

Animal Feed↗
PubMed1990

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.

Breast Feeding↗
PubMed1990

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.

Adolescent↗