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Biomedical subjects

P Ireland

Publications and source records attributed to P Ireland.

At least 19 recordsLinked to original sources

The Anti Cancer Council of Victoria FFQ: relative validity of nutrient intakes compared with weighed food records in young to middle-aged women in a study of iron supplementation.

OBJECTIVE: To assess the validity of the Anti Cancer Council of Victoria food frequency questionnaire (ACCVFFQ) relative to seven-day weighed food records (WFRs) in 63 women of child-bearing age. METHOD: 63 women completed WFRs to assess iron intake as part of a study on iron deficiency. These women also completed the ACCVFFQ. Nutrient intakes were computed independently for the WFRs and FFQs. Intakes were compared as group means, by correlation and by quintile classification, adjusting for day-to-day variation in intakes, and for energy intake. Individual differences in results were also examined. RESULTS: The strongest associations between WFR and FFQ results were energy-adjusted, log-transformed and adjusted for day-to-day variability in intake. Correlation coefficients ranged from 0.28 for vitamin A to 0.78 for carbohydrate. Mean intakes from the WFRs and FFQs were within +/- 20% for 21 of 27 nutrients. Poor agreement between FFQs and WFRs for retinol intake was due to the inclusion of liver in two WFRs, an item which is not included in the FFQ. CONCLUSION: The ACCVFFQ performs as well as other FFQs for which validation data are available. The relatively poor measurement of retinol is consistent with other data, and with the limited number of foods in which this nutrient is abundant. IMPLICATIONS: The availability of an optically scannable valid instrument for assessing dietary intake will facilitate epidemiological studies of diet and disease, an area of current research priority.

Adolescent↗

Isolation and characterization of a unique sulfated ganglioside, sulfated GM1a, from rat kidney.

A novel class of sulfoglycosphingolipid, a sulfate analog of ganglioside, was isolated from mammals for the first time. This sulfated ganglioside was purified from rat kidney by column chromatographies on anion exchangers and silica beads. One-dimensional 1H NMR, compositional and permethylation analyses showed that this glycolipid has a Gg4Cer core with 1 mol each of sulfate ester and N- glycolylneuraminic acid (NeuGc) at C-3 of galactose. The major ceramide consisted of nonhydroxy fatty acids (24:0 and 22:0) and 4-hydroxysphinganine (t18:0), deduced from the compositional analysis and negative liquid secondary ion mass spectrometry (LSIMS). Mild acid hydrolysis and solvolysis produced compounds which correspond to Gg4Cer IV3-sulfate (SM1b) and II3NeuGcalpha-Gg4Cer (GM1a (NeuGc)), respectively. The abundant ions characteristic for sulfated mono- and disaccharides in high-energy collision-induced dissociation (CID) spectra were consistent with the structure at the non-reducing terminus, HSO3 -O- Hex -O- HexNAc- rather than the alternative structure, NeuGc -O- Hex -O- HexNAc-. The two-dimensional 1H NMR further evidenced the presence of a 3 -O- sulfated galactose in the molecule. From these results the complete structure was proposed to be HSO3-3Galbeta-3GalNAcbeta-4(NeuGcalpha-3)Galb eta-4Glcbeta-1Cer (II3NeuGcalpha-Gg4Cer IV3-sulfate).

Animals↗

Diet, nutrition and prostate cancer.

Although much has been written, little is known about the causes of prostate cancer. Variations between populations in the incidence of invasive cancers, together with changes in the incidence of invasive cancers in migrants, have pointed to environmental (lifestyle) factors that might be amenable to intervention. Conversely, there is a lack of international variation in the prevalence of microscopic tumours, so the essential question is: what causes only some of the common microscopic tumours to become aggressive? Dietary factors hold the most promise in this regard and have been the subject of recent reviews. The strongest and most consistent effects are positive associations with animal products such as red meats, eggs and dairy foods, and possibly by implication, fat. Evidence of a protective effect of fruit and vegetables is weak and inconsistent, as is the relationship with vitamin A and carotenoids, such as beta-carotene. There are some interesting leads. Lycopene, the carotenoid found in tomatoes, has been reported to be protective; alpha-tocopherol supplementation has shown a protective effect in one intervention study; and vitamin D has been shown to be protective in a prospective study. Interest is also growing in phytoestrogens and the extent to which dietary manipulation with these and other phytochemicals might influence prostate cancer by modifying male sex hormone levels or actions. There is limited evidence of associations with obesity. It is not known whether these are related to a particular dietary pattern or to possible physiological effects on the male's hormonal milieu. Associations with lean body mass are likely to be related to the action of androgens during growth and development. Dietary and nutritional effects on prostate cancer do not appear to be strong, but they may be subtle and attenuated by measurement error. To explore these aspects further will require large prospective studies that include improved (repeated) dietary measurements and also blood sampling, so that genetic polymorphisms can be adequately investigated. Such studies are underway.

Alcohol Drinking↗

Structural characterization of a novel mono-sulfated gangliotriaosylceramide containing a 3-O-sulfated N-acetylgalactosamine from rat kidney.

A novel mono-sulfated glycosphingolipid based on the gangliotriaose core structure was isolated from rat kidney. The isolation procedure involved extraction of lipids with chloroform/methanol, mild alkaline methanolysis, column chromatographies with anion exchangers and silica beads. The structure was characterized by compositional analysis, FTIR spectroscopy, methylation analysis, 1H-NMR spectroscopy and negative-ion liquid secondary ion mass spectrometry (LSMIS) using the intact glycolipid and its desulfation product. The two dimensional chemical shift correlated spectroscopy provided information on the sugar sequence as well as anomeric configurations, and indicated the presence of a 3-O-sulfated N-acetylgalactosamine within the molecule. Negative-ion LSIMS with high- and low-energy collision-induced dissociation defined the sugar sequence and ceramide composition, confirming the presence of a sulfated N-acetylgalactosamine at the non-reducing terminus. From these results, the complete structure was proposed to be HSO3-3GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer (Gg3Cer III3-sulfate, SM2b).

Acetylgalactosamine↗

Structural analysis of mono- and bis-sulfated glycosphingolipids by negative liquid secondary ion mass spectrometry with high- and low-energy collision-induced dissociation.

Several underivatized mono- and bis-sulfated glycosphingolipids having gangliotriaose or gangliotetraose core structure were analyzed by negative liquid secondary ion mass spectrometry (LSIMS) with high- and low-energy collision-induced dissociation (CID). In the normal negative LSIMS spectra, each mono-sulfated glycolipid gave abundant [M - H]- ions and each bis-sulfated glycolipid gave abundant [M + Na - 2H]- ions as well as the hydrogen sulfate anion [OSO3H]-. In high-energy CID spectra of the deprotonated molecule, only ions containing a sulfate ester were clearly observed. When a sulfate was present on the non-reducing terminal saccharide residue, a series of ions corresponding to sulfated mono- to tetra-saccharides, resulting from sequential cleavage of glycosidic bonds, were observed. If the sulfate was attached to an internal hexose of the sugar chain, the product ions corresponding to the non-sulfated, non-reducing terminal residue were absent. In contrast, the low-energy CID resulted in extremely simple spectra that contained only one or two major product ions characteristic of each sulfated glycolipid. These results provided clear information on the overall sugar and ceramide compositions, and allowed saccharide structures differing in location and number of sulfate esters to be distinguished.

Animals↗

Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation.

The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.

Adolescent↗

A novel mono-sulfated pentaglycosylceramide with the isoglobo-series core structure in rat kidney.

A five-sugar sulfated glycosphingolipid containing an isoglobo-series carbohydrate core was isolated from rat kidney and its structure characterized by compositional analysis, FTIR spectroscopy, methylation analysis and 1H NMR spectroscopy of the intact glycolipid and its limited degradation products, and negative liquid secondary ion mass spectrometry (LSIMS). The two dimensional chemical shift correlated spectroscopy and NOE spectroscopy provided information on the sugar sequence and linkage as well as anomeric configurations, so as to establish the presence of a 3-O-sulfated galactose and a Gal alpha 1-3Gal structure within the molecule. Negative LSIMS with collision-induced dissociation defined the sugar sequence and ceramide composition, allowing to confirm the presence, and indicating the position, of the sulfate group. The glycosphingolipid was found to be a mono-sulfated derivative of the isoglobo-series core, with the following structure: HSO3(-)-3Gal beta 1-3GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Glc beta 1-1Cer (iGb5Cer V3-sulfate).

Animals↗

An increased HLA DR2 frequency is seen in aplastic anemia patients.

The underlying etiology of aplastic anemia is unknown in the majority of patients, although medications, chemical exposure, or viral infections can be implicated in some. Genetic susceptibility to a variety of diseases has been shown and it has recently been suggested that aplastic anemia is more common in individuals who are HLA DR2+ than in the general population. To examine this question, we retrospectively analyzed the results of HLA-DR typing in 75 aplastic anemia patients who received antithymocyte globulin (ATG) therapy or an HLA-matched sibling bone marrow transplant at UCLA between 1978 and 1989. Thirty-one patients were DR2+, a 1.9-fold higher incidence than the expected number of 16.6 patients (P < .0005). Of the 37 patients who received ATG, 33 were evaluable for a response; 14 patients had either a complete (4 patients) or partial (10 patients) response, for an overall response rate of 42.4%. Of the 14 DR2+ patients who received ATG, 7 responded, for a 50% response rate, which is not significantly higher than the response rate for the DR2- patients (7 of 19 [36.8%]; P = .50). The median survival of patients who are DR2+ was slightly, but not significantly, longer than that of the DR2- patients in the ATG group (P = .19). Although the incidence of HLA DR2 was clearly increased in these patients with aplastic anemia, response rates to ATG were not significantly different in the DR2+ and DR2- patients.

Adolescent↗

A phase I/II study of interleukin-3 in patients with aplastic anemia and myelodysplasia.

We performed a phase I/II study of recombinant human interleukin-3 (rhIL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS). Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 micrograms/kg/d) by subcutaneous injection followed by a 10- to 14-day washout period. Nineteen patients completed at least one 21-day cycle of IL-3. Frequent toxicities of IL-3 included headache, low-grade fever, and erythema at the injection site; at higher doses, weight gain and peripheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil counts (seven with MDS, one with AA) including six of the nine patients receiving > or = 5.0 micrograms/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had decreased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multilineage effects were seen in only 25% of patients with primary bone marrow failure states (five of 20 evaluable) and more commonly in patients with myelodysplastic syndromes. Its optimal use may be as part of combination hematopoietic growth factor therapy.

Adult↗

Short-term effects of alterations in dietary fat on metabolic control in IDDM.

OBJECTIVE: Two experimental diets were evaluated to investigate the hypothesis that dietary fat has an independent influence on metabolic control in IDDM. RESEARCH DESIGN AND METHODS: The diets had similar CHO contents (26 and 22% of energy intake) but differed markedly in fat (53 vs. 16% energy) and protein (20 vs. 62% energy). We had 10 subjects follow the low-CHO, high-fat diet, and 8 subjects follow the low-CHO, low-fat, high-protein diet. In each case, markers of glycemic and lipid control obtained after adherence to the experimental diet for 2 wk were compared with corresponding data from a preceding control period during which subjects had followed their usual diet (protein 18-19%, CHO 41-46%, fat 33-37%). RESULTS: Despite the low CHO content of the high-fat diet, insulin requirements were unchanged relative to the control diet. Moreover, the glycemic response to a standard breakfast was elevated significantly (P < 0.001), suggesting that insulin resistance had either been induced or exacerbated. The small rise in total cholesterol concentration in response to the high-fat diet was accounted for by a rise in HDL cholesterol. Glycemic control and lipid metabolism were unchanged after the low-CHO, low-fat diet, although insulin requirements fell by an average of 6 U/day (P < 0.05) relative to those recorded during the 2-wk control period. CONCLUSIONS: Diets high in fat are deleterious to glycemic control in IDDM, but general applicability is limited by the small sample size and short duration of this study.

Adult↗

Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor.

Fifteen patients with refractory aplastic anemia or agranulocytosis received treatment with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) in doses from 4 to 64 micrograms/kg/d by continuous intravenous (IV) infusion. Ten of 11 evaluable patients with aplastic anemia had substantial increments in granulocytes, monocytes, and eosinophils associated with myeloid and eosinophilic hyperplasia in the bone marrow. Patients with pretreatment granulocytes greater than 0.3 x 10(9)/L had greater increments in circulating myeloid cells than patients with more severe granulocytopenia. Only one patient had improvement in erythrocytes and platelets. Blood counts fell to baseline after rhGM-CSF treatment was discontinued. Doses up to 16 micrograms/kg/d were relatively well tolerated in the absence of extreme leukocytosis. Fatigue and myalgia were common. Three patients developed pulmonary infiltrates that resolved with discontinuation of treatment. Patients tended to have recurrent inflammation in previously diseased tissues. These data indicate that rhGM-CSF will increase circulating granulocytes, monocytes, and eosinophils in patients with refractory aplastic anemia. Further studies are necessary to determine if rhGM-CSF treatment will reduce morbidity or improve survival.

Anemia, Refractory↗

The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes.

This study was designed to determine the effects of varying the proportions of carbohydrate, fiber, and fat on metabolic control in Type II diabetes. Ten men, aged 50 to 69 years, with Type II diabetes participated. Four isocaloric diets were consumed for 2 weeks each, with a break of 6 to 14 weeks between diets to ensure no carryover effects. Two of the diets were high in carbohydrate (63% to 65% energy) and low in fat (10% to 12% energy) but differed in their fiber contents (20 vs. 45 gm/day). The other two diets were low in carbohydrate (23% to 27% energy) with either a low or a high fat content (15% vs. 55% energy) and a high or normal protein content (62% vs. 18% energy). The composition of the subjects' usual diets in the week before each of the experimental diets did not vary significantly: carbohydrate 47% to 50% energy, protein 22% to 25% energy, fat 27% to 31% energy, and fiber 24 to 25 gm/day. A 75-gm oral glucose tolerance test and a 12-hour metabolic profile in response to 3 meals typical of the particular diet were conducted before and at the conclusion of each 2-week dietary period. The most significant improvements in metabolic control (as assessed by the effects of the diets on fasting glucose and on lipids, and on the glucose and insulin responses to oral glucose and the mixed meals) were obtained with the high-fiber, high-carbohydrate, low-fat diet and with the low-carbohydrate, high-protein, low-fat diet. Metabolic control was not significantly affected by the low-fiber, high-carbohydrate, low-fat diet, but it deteriorated significantly on the low-carbohydrate, high-fat diet. The results of this study confirmed the importance of high fiber and low fat in improving metabolic control in Type II diabetes. In conclusion, if high-carbohydrate, low-fat diets are to be recommended to patients with diabetes, it is essential that the type of carbohydrate recommended be unrefined and high in fiber.

Blood Glucose↗

Plasma glucose levels in the peri-operative period in children.

Peri-operative plasma glucose levels were studied in one hundred children under 5 years of age and under 20 kg. All underwent procedures of less than 30 minutes. Of 32 cases under the third percentile for weight, ten developed low plasma glucose during the pre-operative and/or postoperative phase. This occurred despite receiving 5% dextrose by mouth 4 hours before induction. Even in children of normal weight there was a low incidence of peri-operative hypoglycaemia. Routine intravenous glucose-containing fluids are thus recommended during the peri-operative period.

Anesthesia↗

Effect of dietary calcium and age on jejunal calcium absorption in humans studied by intestinal perfusion.

Jejunal calcium absorption was measured from test solutions containing 1.0, 2.5, 5, and 10 mM calcium (as calcium gluconate). Absorption rates increased progressively as luminal calcium concentration was increased, although there was a tendency toward saturation of the absorptive process at the higher concentrations. Calcium absorption was higher in normal young adults than in normal subjects over age 60. In both groups a 300 mg calcium diet for 4-8 wk enhanced calcium absorption relative to absorption rates after 4-8 wk on a 2,000 mg calcium diet. This adaptation was more definite and dramatic in the young than in the old subjects. Indirect estimates suggest that adaptation to a low calcium diet and the higher absorption in young than old normal subjects are mediated by an increased V(max) rather than a decreased K(m).

Adult↗