Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United kingdom.

Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.

Prognostic significance of chromosome 17p deletions in childhood primitive neuroectodermal tumors (medulloblastomas) of the central nervous system.

Deletions in the short arm of chromosome 17 (17p) are the most common genetic abnormality in primitive neuroectodermal tumors of the posterior fossa/medulloblastoma (PNET/Mb). The biological consequences of these deletions are not known for children with PNET/Mb; however, the presence of a tumor suppressor gene located in 17p, distinct from p53, has been implicated in tumorigenesis. Two recent studies suggest that 17p deletions in PNET/Mb are associated with a poor prognosis. To address this question, we identified deletions of chromosome 17p by cytogenetic and/or molecular biology methods in tumor biopsy samples from 56 patients with PNET/Mb. Associations between clinical characteristics or survival outcomes and 17p status were examined by multivariate analysis. Forty-one percent of PNET/Mb cases had a deletion of 17p. No significant association was found between 17p deletion and shorter survival duration or higher metastatic stage. Multivariate analysis did not find independent prognostic significance for 17p deletions after accounting for the effects of significant clinical variables. A larger study of the prognostic value of 17p deletion should be considered; however, clinical use of this factor to distinguish high-risk from standard-risk PNET/Mb populations is not warranted at this time.

Effect of income and geographic region on the nutritional value of diets in Brazil.

The nutritional quality of dietary patterns in Brazil was examined as influenced by income level, region, and urbanization by calculating nutrient to calorie ratios and amino acid scores. In general, income level had only a minor influence on diet quality. Riboflavin and calcium were generally low in the low income groups in all regions, especially in urban areas. Thiamin intake was marginal in urban areas at all income levels. Protein quality appeared to be relatively independent of income, with two exceptions. These were the dietary patterns of the lowest income groups in the rural Northeast and the City of Sao Paulo which were somewhat limiting in methionine and lysine, respectively. In contrast, the total availability of calories and protein was greatly dependent on income and the lowest income families were seriously short of food. Income, therefore, appeared to be more important in determining the total amount of food available to a family in Brazil than in affecting the nutritional quality of the diet.

Questionnaire assessment of intake of specific carotenoids.

We determined whether estimation of intake of specific carotenoids with a standard food-frequency questionnaire (FFQ) could be improved by collection of additional data on the intake of carotenoid-rich food items. The foods included on an addendum to the standard FFQ were potentially important dietary contributors of alpha- and beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, or lycopene. Participants (n = 215), ages 50-74 years, provided fasting blood samples and completed the FFQ and the addendum. The participants were enrolled in a prepaid health plan and had undergone screening sigmoidoscopy for detection of colorectal polyps. Addendum foods were identified that accounted for variation in blood levels of specific carotenoids, conditional on intake of foods on the standard FFQ. Estimated carotenoid intakes from the standard FFQ, and from the modified FFQ with the selected addendum foods, were examined in relation to plasma carotenoid levels. The correlation coefficient between estimated carotenoid intake and plasma levels (adjusted for age, sex, serum cholesterol, alcohol intake, smoking status, and energy intake) were essentially the same for the standard and modified FFQs. The adjusted correlations for the standard FFQ only were 0.26 for alpha-carotene, 0.22 for beta-carotene, 0.36 for beta-cryptoxanthin, 0.32 for lutein+zeaxanthin, and 0.34 for lycopene. Adding carotenoid-rich foods to the FFQ did not improve estimation of intake for the carotenoids examined in this population. We conclude that assessment of intake of specific carotenoids with the FFQs currently in use may not necessarily be improved by a modified list of carotenoid-rich foods.

Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas.

We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

Changes in protein metabolism of ovine primary muscle cultures on treatment with growth hormone, insulin, insulin-like growth factor I or epidermal growth factor.

Methods for the primary culture of muscle cells from fetal sheep were developed which gave high yields of cells. Myoblasts were grown in vitro, and allowed to fuse to form contractile multinucleate myotubes; these could be maintained in a good condition for at least 2 weeks. Protein turnover in these differentiated cultures was examined for sensitivity to each of four potentially anabolic peptide hormones and growth factors: insulin, insulin-like growth factor I (somatomedin C), epidermal growth factor and growth hormone. Insulin was found to have no effect except at high concentrations (1 mumol/l), compatible with its role as a somatomedin analogue. Insulin-like growth factor I was active at lower levels (1 nmol/l) but the cultures were not as responsive to it as were primary rat muscle cultures or differentiated L6 cells, which were tested in similar experiments. The maximum stimulation of protein synthesis observed with the ruminant system was only 16%. Epidermal growth factor was highly anabolic for primary cultures from sheep muscle, and the cells were very sensitive to it, half-maximal stimulation of protein synthesis being seen with concentrations as low as 20 pmol/l. No effects of bovine growth hormone were seen in the ovine system. However, an inhibition of protein breakdown was found with high concentrations (0.1 mumol/l) in the L6 rat myoblast cell line. It was found that the culture conditions used could affect the observed responses of protein synthesis and degradation, despite withdrawal of serum from the incubation media 22 h before testing.

Protein metabolism in ovine primary muscle cultures derived from satellite cells--effects of selected peptide hormones and growth factors.

Methods were developed for the isolation and culture of satellite cells from adult sheep muscle. Differentiated cultures of these cells were used to investigate the effects of four hormones and growth factors on protein synthesis and degradation. Insulin was found to have no effect except at supraphysiological concentrations (100 nmol/l and 1 mumol/l) where it is probably crossreacting with the insulin-like growth factor (IGF) type-I receptor. IGF-I was found to be anabolic at lower concentrations (1-3 nmol/l). Epidermal growth factor (EGF) had a smaller effect on protein synthesis and degradation than insulin or IGF-I. The specific activity of the muscle-specific enzyme creatine phosphokinase (CPK) was increased by treatment with EGF. When both IGF-I and EGF were present in the test media an additive effect on protein synthesis was observed. However, no additive effect of IGF-I and insulin was noted. No effects of bovine GH were seen.

Beta-adrenoceptors and the effect of beta-agonists on protein metabolism in ovine primary muscle cultures.

The beta-adrenergic receptors of differentiated ovine muscle cultures derived from either fetal or pre-pubertal lambs were characterized by binding of (+/-)-[3H]CGP-12177, directly to intact cells in monolayer. Fetal muscle cells contained a single class of specific and saturable binding sites which had a dissociation constant (Kd) of 0.38 x 10(-9) M and a binding capacity of 55.2 fmol/micrograms protein. beta-Adrenergic agonists competed for the specific binding sites with a typical beta 2-adrenergic specificity. Satellite muscle cells derived from pre-pubertal lambs contained two classes of binding site. The high affinity site had a Kd of 1.02 x 10(-9) M and a binding capacity of 28.4 fmol/micrograms protein and the low affinity site a Kd of 12.1 x 10(-9) M and a binding capacity of 389 fmol/micrograms protein. beta-Adrenergic agonists competed for the specific binding sites with a typical beta 1-adrenergic specificity. The beta-agonist cimaterol had no effect on either protein synthesis or degradation in fetal muscle cells. In cultures derived from satellite cells cimaterol significantly stimulated protein synthesis at concentrations of 10(-8) - 10(-7) M and at 10(-8) - 10(-6) M in the presence of serum. These effects were maintained if 10(-5) M propranolol was added to the incubation media, but were blocked by 10(-6) M isoproterenol. Propranolol and isoproterenol had no stimulatory effects on protein synthesis. Cimaterol also had no detectable effects on protein degradation or the transport of amino acids or glucose. It is concluded that although beta-adrenergic receptors are present in ovine muscle cultures they may not play a role in the anabolic effect of beta-agonists observed in cultured muscle cells.

Beneficial effects of non-depleting anti-CD4 in MRL/Mp-lpr/lpr mice with active systemic lupus erythematosus and microscopic angiitis.

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop lymphoproliferation and systemic autoimmune disease. The majority of mice in any cohort develop systemic lupus erythematosus (SLE) and up to a quarter of them develop a syndrome that resembles microscopic angiitis (MPA). Both conditions are characterized by vasculitis, glomerulonephritis and autoantibody formation. Depleting anti-CD4 monoclonal antibody (mAb) treatment is ineffective in MRL/lpr mice after disease onset. The present study investigates the effects of a non-depleting anti-CD4 mAb in MRL/lpr mice with active SLE or MPA. This antibody increased survival compared to control Ig but did not prolong survival compared to non-treated mice. However, anti-CD4 significantly reduced lymphoproliferation in the mice and furthermore reduced the vasculitis component of the autoimmune disease following several weeks of treatment.

Factors involved in the pathogenesis of neutrophilic vasculitis in MRL/Mp-lpr/lpr mice: a model for human microscopic angiitis.

Anti-neutrophil cytoplasm antibodies (ANCA) directed against myeloperoxidase (MPO) are detected in patients with microscopic angiitis. Human MPO autoantibodies stimulate neutrophil degranulation in vitro and are thought to be pathogenic. We have previously shown that MRL-lpr mice with MPO autoantibodies have a higher incidence of vasculitis than their seronegative littermates. The aim of the present study is to determine the relationship between MPO autoantibodies and microscopic angiitis. The neutrophil binding properties of anti-MPO monoclonal antibodies (mAbs) from MRL-lpr mice were tested using murine heterophils (neutrophils) present in blood and induced peritoneal exudates. MRL anti-MPO mAbs selectively bind activated neutrophils which express MPO in vitro. The pathogenicity of an IgG2b anti-MPO mAb, C6, was investigated in vivo. Anti-MPO mAb, C6 was administered to young MRL mice which had been primed with exogenous TNF alpha to induce neutrophil activation and expression of MPO. Neutrophilic vasculitis similar to microscopic angiitis occurred in 33% of MRL mice which had been treated with anti-MPO mAb. The lesions were mainly restricted to sites of previous endothelial insult which suggests an active role for injured endothelium in this pathology.

A locus on chromosome 2 influences the development of acute graft-versus-host disease in a murine model.

Despite contemporary typing procedures for bone marrow transplantation (BMT), graft-versus-host disease (GVHD) continues to be a major complication of transplants performed between MHC-matched donors and recipients. Although GVHD can be alleviated by T cell depletion, this procedure increases the risk of graft failure and leukemic relapse and therefore is not a solution to the GVHD problem. The high degree of variation in the intensity of GVHD observed in different patients suggests that multiple non-MHC genetic factors influence GVHD severity. We hypothesize that, in addition to minor histocompatibility antigen disparities, polymorphisms in genes encoding immunologic effector molecules may be important factors influencing GVHD development. This study aims to explore this hypothesis by identifying non-MHC genes that influence the outcome of BMT in a murine model. In this model, B10.D2 donor leukocytes cause acute GVHD in (C57BL/6xDBA/2)F1 (B6D2F1) recipients, whereas DBA/2 donor leukocytes do not. To date, a locus on chromosome 1 has been identified as influencing the severity of GVHD in this model. Our current study shows that a locus on chromosome 2 acts independently of the chromosome 1 locus to also influence GVHD severity in this model. The region of chromosome 2 implicated in our study contains genes encoding beta2-microglobulin, the minor histocompatibility antigen H-3 and the pro-inflammatory cytokine IL-1.

Genetic factors influencing the development of chronic graft-versus-host disease in a murine model.

Graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation that can occur in either acute or chronic forms. Much of the long-term pathology seen in chronic GVHD is a result of autoantibody production. In the DBA/2-->B6D2F1 murine model of chronic GVHD, anti-ssDNA autoantibodies can be detected by 14 days post cell transfer. These autoantibodies are not observed in B6D2F1 recipients of cells from C57BL/6 or B10.D2 donors, which develop acute rather than chronic GVHD. Therefore, in this model, donor genetic factors predispose to the development of chronic GVHD in recipients. We performed a genetic analysis aimed at mapping donor loci that influence the magnitude of early autoantibody production in B6D2F1 recipients of cells from DBA/2 donor mice. Linkage analysis suggested an influence of two loci: a locus on chromosome 11 linked to D11Mit278 and a locus on chromosome 4 linked to D4Mit226. The locus on chromosome 11 also appeared to influence the development of renal pathology associated with chronic GVHD.

Analysis of physical parameters associated with the measurement of high-energy x-ray penumbra.

The effect of dosemeter type and configuration on the measured penumbral distribution for Co-60, 6-MV, and 31-MV x rays has been determined in air using equilibrium buildup caps for three commercial detection systems including a silicon diode and two ionization chambers. The diode is shown to be measuring a different parameter in the penumbral region than the ionization chambers. This fact in combination with the lateral spread of the secondary electrons and the difference in the inside diameters of the ionization chambers results in significant differences between the measured beam penumbra. The latter effect is studied in more detail with a series of specially designed ionization chambers of varying inside diameter from 0.3 to 1.4 cm. A theoretical model is described which resolves these differences, indicates a method to determine the true penumbral primary-dose distribution and introduces the concept of an effective diameter for the ionometric measurement of high-energy x-ray penumbra. Recommendations are made concerning the dosemeters of choice for penumbral measurements over this range of photon energies.

Consumption and plate waste of menu items served in the National School Lunch Program.

Plate waste was determined in fifty-eight elementary and high schools in the USDA Western, Midwestern, and Southwestern Regions. By weighing sample trays and edible waste, the percentage of food served that was consumed was measured for 23,000 lunches. Highest consumption was recorded for milk, with 88 and 94 per cent consumed in the fifth and tenth grades respectively. Most entrées and starches were well consumed; vegetables and salads showed much less acceptability. Regional differences in food acceptability were minor, and high school students consistently wasted less food in all categories than did elementary pupils.

Alternate lunch patterns in high schools. II. Student and foodstaff reactions.

Reactions to alternate menu patterns used in high school lunches were measured. Students rated food in Basic 4 and free-choice patterns more positively than Type A. The environment in the lunchroom was not rated differently with different menu patterns. Based on overall student reactions, the free-choice pattern was preferred. School lunch managers found the free-choice pattern more difficult to serve because of reimbursement and pricing problems but felt there was less plate waste and better student response with this system.

Alternate lunch patterns in high schools. III. Food acceptability.

Food acceptability was assessed in forty-eight high schools using alternate methods of menu planning for school lunches. The free-choice pattern resulted in a significant reduction of total plate waste, particularly in the vegetable and salad categories. Girls consistently wasted more food than did boys, regardless of menu pattern. Overall plate waste was 7 and 13 per cent of food service for boys and girls, respectively. The data suggest that a free-choice lunch may be effective in reducing plate waste, particularly for poorly consumed menu items.

Alternate lunch patterns in high schools. I. Labor requirements and meal costs.

Meal costs were compared in forty-eight high schools as a function of the lunch pattern. The patterns evaluated were: Type A "offer vs. serve," traditional Type A, four food groups (Basic 4), and free choice. Participation in school lunch increased with free choice, resulting in a reduction in labor and total meal costs. Sixteen per cent of foodservice work involved administration, 37 per cent preparation, 16 per cent service, 25 per cent clean-up, and 6 per cent other, which did not vary with the menu pattern.

Menu planning in the Nutrition Program for the Elderly. Modified Nutrient Standard Menu method.

A nutrient standard menu (NSM) planning method was developed for use in planning menus which provided one-third the Recommended Dietary Allowances for persons sixty years of age or older for nine indicator nutrients and calories, while restricting fat to less than 40 per cent of total calories. To eliminate manual calculations and make it easy for individuals untrained in dietetics or nutrition to use NSM planning, the nutrient composition of over a thousand commonly used menu items was listed in a menu planning manual in nutrient units which were one-tenth of the nutrient standard for the meal. Menus from third-party sources were monitored by selecting similar nutritionally analyzed menu items in the manual and adjusting the nutrient composition to conform to the portions actually served. Ten site managers of the Administration on Aging (AoA) evaluated the planning/monitoring method. The members of the group, on the average, were fifty-six years of age, had 1.6 years of education beyond high school, and had 4.6 years of foodservice experience. Approximately 83 per cent of the evaluators did not plan to monitor menus at their sites and had no formal training in dietetics or nutrition. Eighty-four per cent were able to plan menus satisfactorily after this brief introduction. The younger evaluators with more education grasped the concepts faster and were able to plan menus with greater accuracy. The data also indicated that previous experience in menu planning enhanced their ability to plan NSMs. Most felt the approach to be workable and applicable. Menu monitoring was more difficult for the evaluators. Seventy-five per cent were able to monitor menus satisfactorily, and all felt they could do so with more time. The data again showed that the younger individuals having more formal education were able to master the monitoring skills more easily.

Alternate lunch patterns in high schools. IV. Nutritive value.

The nutritive value of lunches in forty-eight high schools was assessed using alternate methods of menu planning. Using Type A, Basic 4, and free-choice patterns, the nutrient levels in lunches consumed were not significantly different from those of lunches using the Type A "offer vs. serve" pattern. For boys, lunches as consumed were significantly below the goals for calories, thiamin, and iron in all groups. For girls, lunches as consumed were significantly below the goal only for iron.

Comparison of Type A and nutrient standard menus for school lunch. I. Development of the nutrient standard method (NSM).

Methodology was developed for planning school lunch menus which meet a specific nutrient standard. The method considered nine indicator nutrients plus calories and percentage of calories coming from fat. The nutrient composition of approximately 625 school lunch menu items were calculated using Agriculture Handbook No. 8 data. All nutrient data were converted to bead units which were summed on an abacus until the meal requirements were met. Preliminary testing of the method showed it to be usable by school lunch menu planners and provided menus meeting certain minimal nutrient constraints. After the test, suggested modifications were incorporated into the method to enhance its use. The method is described and a sample week's given.