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Biomedical subjects

Yves M Dupertuis

Publications and source records attributed to Yves M Dupertuis.

At least 19 recordsLinked to original sources

Auger radiation targeted into DNA: a therapy perspective.

BACKGROUND: Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of alpha particles. In contrast to alpha radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. DISCUSSION: Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided alpha and beta radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation.

DNA Damage↗

Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells.

OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multivariable linear regression analyses were used for comparison. RESULTS: Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 micromol/L vitamin E abolished the effect of 50 micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.

Adenocarcinoma↗

Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine.

PURPOSE: Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations. METHODS: Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment. RESULTS: The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline. CONCLUSION: FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.

Cell Cycle↗

Ergonomic and economic aspects of total parenteral nutrition.

PURPOSE OF REVIEW: Ergonomics in total parenteral nutrition include the work performed in the (hospital) pharmacy and on the medical ward. This article reviews the developments in total parenteral nutrition ergonomics and the related cost-savings. RECENT FINDINGS: Research focuses on the ergonomic advantages of multi-compartment total parenteral nutrition bags compared with the multi-bottle system, of multi versus single-layered total parenteral nutrition bags and of the presence of a nutritional team and training in clinical nutrition to improve regimen prescription and delivery. SUMMARY: Three-compartment bags are safe, economic and ergonomic. It is important, however, to keep the knowledge of pharmacies to compound total parenteral nutrition for children and (adult) patients with specific pathologies. Research is ongoing in the development of bags with more than three compartments, to include for instance vitamins. This necessitates improvements in bag materials and wrapping. Progress can be made regarding total parenteral nutrition prescription and delivery, as well as in the incidence of related infections by promoting training in clinical nutrition and the implementation of a multidisciplinary nutritional support team.

Critical Illness↗

Comparison of fat-free mass and body fat in Swiss and American adults.

OBJECTIVE: No current studies have compared North American with European body composition parameters, i.e., fat-free mass (FFM), body fat (BF), and percentage of BF (%BF) in large populations. This study compared FFM, BF, and %BF values derived from two bioelectrical impedance analysis (BIA) equations (Geneva and National Health and Nutrition Examination Survey [NHANES]) in Swiss subjects and compared FFM, BF, and %BF values of white Swiss with those of white North American adults with the same BIA equations. METHODS: Healthy adults (3714 men and 3199 women), ages 20 to 79 y, in Switzerland were measured by single-frequency BIA and compared with means and standard deviations for body mass index and body composition parameters obtained from the NHANES III study (United States; n = 2538 men, 2862 women). FFM was calculated with the Geneva and NHANES equations. RESULTS: Mean FFMGENEVA values did not differ from FFMNHANES values in men but was significantly lower (-1.5 kg) in women. FFM and BF values in American men, who weighed 4.2 to 12.0 kg more than the Swiss men, were significantly higher (+2.1 to +6.0 kg and +1.5 to +6.4 kg, respectively) than those in the Swiss men. FFM and BF values in American women, who weighed 2.3 to 12.1 kg more than the Swiss women, were significantly higher (+1.3 to +2.1 kg and +4.8 to +11.8 kg, respectively, except FFM in subjects ages 20 to 29 y and BF in those ages 70 to 79 y) than FFMGENEVA values in Swiss women. FFM in American women was significantly lower (+1.3 and +1.9 kg) and non-significantly higher than FFMNHANES in Swiss women. CONCLUSION: NHANES and Geneva BIA equations estimate body composition equally well in men, but further research is necessary to determine the discrepancies in FFM between BIA equations in women. The greater weight of the American subjects yielded higher values for FFM, BF, and %BF in American than in Swiss men and women.

Adipose Tissue↗

n-3 polyunsaturated fatty acids and colon cancer prevention.

The incidence of colon cancer in industrialised countries has increased since the early 1970s. It is estimated that more than one-third of cases are associated with factors related to a Western diet. Both the type and amount of dietary fats consumed have been implicated in colon cancer aetiology. Recent studies have demonstrated that n-3 polyunsaturated fatty acids (PUFAs), commonly found in fish oil (FO), could prevent colon cancer development. Evidences show that n-3 PUFAs act at different stages of cancer development and through several mechanisms including the modulation of arachidonic acid-derived prostaglandin synthesis, and Ras protein and protein kinase C expression and activity. As a result, n-3 PUFAs limit tumour cell proliferation, increase apoptotic potential along the crypt axis, promote cell differentiation and possibly limit angiogenesis. The modulatory actions of n-3 PUFAs on the immune system and their anti-inflammatory effects might also play a role in reducing colon carcinogenesis. There remains, nevertheless, some ambiguity over the safety of n-3 PUFAs with respect to secondary tumour formation. However, it appears that n-3 PUFAs may be of use in colon cancer prevention.

Animals↗

Higher calorie prescription improves nutrient delivery during the first 5 days of enteral nutrition.

AIMS: It is unclear whether prescribing a higher amount of calories by enteral nutrition (EN) increases actual delivery. This prospective controlled study aimed at comparing the progression of EN of two study populations with different levels of calorie prescriptions, during the first 5 days of EN. METHODS: The daily calorie prescription of group 1 (n=346) was 25 and 20 kcal/kg body weight for women <60 and > or =60 years, respectively, and 30 and 25 kcal/kg body weight for men <60 and > or =60 years, respectively. The prescription of group 2 (n=148) was 5 kcal/kg body weight higher than in group 1. Calorie intakes were expressed as percentage of resting energy expenditure (REE) and protein intakes as percentage of requirements estimated as 1.2 g/kg body weight/day. Patients were classified as <60 and > or =60 years and as medical or surgical patients. Statistical analysis was performed with ANOVA for repeated measures. RESULTS: Calorie and protein deliveries increased in both groups independently of age and ward categories (P< or =0.0001). Group 2 showed faster progressions of calorie and protein intakes than group 1 in patients altogether (P< or =0.002), > or =60 years (P< or =0.01) and in surgical patients (P< or =0.02). Differences of calorie and protein intakes between day 1 and day 5 were significantly higher in group 2 than group 1 for patients altogether (75+/-61 vs. 56+/-54% of REE; 41+/-30 vs. 31+/-/-27% of protein requirements), those over 60 years (76+/-67 of REE vs. 52+/-59 of protein requirements) and surgical patients (81+/-52 vs. 58+/-57% of REE; 44+/-27 vs. 33+/-29% of protein requirements). CONCLUSIONS: Increasing the levels of EN prescriptions improved calorie and protein deliveries. While the mean energy delivery over 5 days was sufficient to cover requirements, the protein delivery by EN was insufficient, despite our nutritional support team.

Analysis of Variance↗

The preparation of clinical grade 5-[123I]iodo-2'-deoxyuridine and 5-[125I]iodo-2'-deoxyuridine with high in vitro stability and the potential for early proliferation scintigraphy.

BACKGROUND AND METHODS: 5-Iodo-2'-deoxyuridine (IdUrd) radiolabelled with the positron emitter I or with the gamma and Auger electron emitters I or I has been proposed for cancer diagnosis and therapy. We modified the synthesis to reliably obtain [I]IdUrd and [I]IdUrd by using an Iodogen supported destannylation reaction of 5-(tri-n-butylstannyl)-2'-deoxyuridine (Bu3SndUrd) which meets the requirements for good laboratory practice (GLP) and good clinical practice (GCP). A method of purification was developed to eliminate by-products as well as any unreacted starting material. RESULTS: [I]IdUrd, which originated from a trace of iodide in the Bu3SndUrd precursor, was identified as the unknown by-product reported for this method. This trace could be eliminated by modified purification of Bu3SndUrd. Stabilization of pH was essential for unequivocal identification of radiolabelled IdUrd and possible degradation products in the different systems tested for quality control. Biodistribution in tumour bearing nude mice was measured as early as 3 and 6 h after i.v. injection of [I]IdUrd. This compound showed high and specific activity uptake in tumour and dividing tissues when combined with 5-fluoro-2'-deoxyuridine pre-treatment. Uptake was specifically inhibited by injection of excess thymidine.

Animals↗

[Simplified malnutrition screening tool: Malnutrition Universal Screening Tool (MUST)].

MUST (Malnutrition Universal Screening Tool) is a nutritional screening tool easy to use by any trained care-giver and valid for any adult patient. It considers body mass index, weight change and acute disease effect equally and determines a malnutrition risk score. If necessary, anthropometric measures may be simpliyfied by alternative methods. MUST is reliable between different healthcare settings et promotes detection and management of malnutrition during the patient medical course.

Acute Disease↗

[Role of impedance measurement in nutritional screening].

Nutritional status has a prognostic value in the clinical evolution of patients who are malnourished, are becoming malnourished or are in process of being rehabilitated. The evaluation of nutritional status is based on a comprehensive approach, and includes body composition measurement by bio-impedance analysis (BIA). BIA determines the quantity of body fat-free and fat mass and has a precision around 4%. The reliability of BIA depends on the use of body composition prediction equations that are adapted to the subjects studied and on the inclusion of various anthropometric parameters (weight, height, sex, age, race, etc). BIA remains imprecise in the presence of abnormal distribution of body compartments (ascites, dialysis, lipodystrophy) or of extreme weights (cachexia, severe obesity). Multi-frequency or segmental BIA were developed to overcome hydration abnormalities and variations in body geometry. However, these techniques require further validation. This review discusses the indications and limitations of BIA.

Anthropometry↗

The role of visceral proteins in the nutritional assessment of intensive care unit patients.

PURPOSE OF REVIEW: This review analyses the recently published literature focusing on nutritional assessment in intensive care unit patients. The metabolic response to nutritional intervention is difficult to evaluate in critically ill patients whose body weight is influenced largely by massive fluid administration or losses. Visceral protein plasma levels have been proposed for this purpose, because they reflect hepatic synthesis in response to nutrient supply. However, in acute inflammatory states, liver activity is converted to the synthesis of acute-phase response proteins, resulting in a dramatic drop in visceral proteins, despite nutritional support. RECENT FINDINGS: The data regarding visceral protein levels were examined in relation to nutritional supplementation, and compared with other nutritional parameters and clinical outcomes. Transthyretin and retinol-binding protein levels seem to be the most sensitive to nutritional intervention. They are also the earliest to rise at the decrease of acute-phase protein levels, therefore representing a good index of the reversing reprioritization of hepatic protein synthesis. An inconsistent relationship was found between visceral protein plasma levels and clinical outcome in intensive care unit patients, probably because of the difficulty in demonstrating clearly a beneficial effect of nutritional supplementation in highly catabolic conditions. SUMMARY: In the acute stage of critical illness, the bi-weekly measurement of transthyretin together with acute-phase response protein plasma levels seems to be a 'window' on the metabolic condition (anabolism versus catabolism). However, only in the presence of stable inflammatory parameters do transthyretin levels reflect the adequacy of nutritional coverage.

Acute-Phase Proteins↗

[Awareness on nutritional problems at hospitals: which solutions?].

Malnutrition is very frequent in hospitalized patients, particularly if they are elderly and suffer of chronic diseases. Many studies show the correlation between the degree of malnutrition and the frequency of complications, the length of hospital stay and the rate of mortality. However, despite the rising interest of scientists for the role of nutrition in the pathogenesis of the diseases, little attention is devoted to the nutritional status of patients. This article reviews the recent literature regarding hospital malnutrition. At hospital admission, 30 to 40% of patients presents a certain degree of malnutrition. However, only a small percentage is recognized to be malnourished and receive an adequate treatment. The reason for this attitude of medical and paramedical teams seems to be a low priority assigned to nutrition. In addition, they seem to lack the most basic knowledge regarding the metabolic needs of their patients. Another finding, reported by several surveys, is that a large portion of hospital food is not consumed by the patients but is wasted. In fact, meals are not sufficiently-adapted to the taste and the appetite of those for whom they are prepared. This article summarizes the recommendation of the Europe Council regarding the nutritional evaluation and treatment of patients.

Hospitalization↗

Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas.

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy.

Animals↗

Body composition in 995 acutely ill or chronically ill patients at hospital admission: a controlled population study.

OBJECTIVE: To determine if fat-free mass and fat mass in acutely ill and chronically ill patients differed from healthy controls at hospital admission and if prevalence of malnutrition differed by body mass index (BMI) or fat-free mass percentile. SUBJECTS/SETTING: 995 consecutive patients 15 to 100 years of age admitted to the hospital were measured in the hospital admission center and compared with 995 healthy age- and height-matched subjects DESIGN: Cross-sectional study. Fat-free mass, fat mass, and percentage fat mass were determined by 50 kHz bioelectrical impedance analysis. Prevalence of malnutrition was determined by BMI < or = 20 kg/m2 or fat-free mass in the 10th percentile. STATISTICAL ANALYSIS: Analysis of variance was used to examine differences between acutely ill and chronically ill patients and controls and between age groups. RESULTS: Fat-free mass was significantly lower in patients than controls (P< or = .05), and the difference with age in fat-free mass in patients was greater than the age-related difference in the controls. A higher percentage fat mass was found in spite of lower BMI in chronically ill patients older than 55 years. Among participants, 25% of acutely ill and 37.3% of chronically ill patients fell below fat-free mass in the 10th percentile, compared with 15.6% of acutely ill and 18.9% of chronically ill patients falling below BMI < or = 20 kg/m2. APPLICATIONS/CONCLUSION: Weight and BMI do not evaluate body compartments and therefore do not reveal if weight changes result in loss of fat-free mass or gain in fat mass. In spite of minimal differences in BMI between patients and controls, we found that fat-free mass was lower and fat mass was higher in acutely ill and chronically ill patients than controls. The objective measurement of body composition, as part of a comprehensive nutritional assessment, helps to identify subjects who have low fat-free mass or high fat mass.

Acute Disease↗

Assessment of nutritional status in organ transplant: is transthyretin a reliable indicator?

Transthyretin has been proposed as a nutritional index to screen for malnutrition and monitor the metabolic response to dietary intervention. In the presence of inflammation, circulating transthyretin levels drop regardless of optimal caloric intake. In this case, due to its rapid turnover, the pattern of transthyretin, monitored by means of repeated measures, could indicate the metabolic status (catabolism vs. anabolism). The aim of this review is to investigate the possible role of transthyretin as a nutritional parameter in organ transplantation. The literature on nutritional assessment in transplantation was reviewed and all the data regarding circulating transthyretin levels were analyzed. It appears that, on the one hand, the transthyretin level reflects closely dietary manipulations; on the other hand, it is affected by the inflammatory status. Consequently, interpretation could be difficult during the acute phase immediately after the transplant. Moreover, the role of transthyretin in monitoring the hepatic synthetic function in liver transplant is discussed. In conclusion, transthyretin is a reliable indicator of nutritional status in transplant candidates and potentially useful in the post-transplant phase if the inflammatory status is taken into account.

Biomarkers↗

[Nutrition and tumoral growth].

Some nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides have been shown to modulate the immune and intestinal systems. They affect the synthesis of proteins and the expression of enzymes, as well as the activation and the proliferation of leukocytes and enterocytes. Since these immunonutrients modulate the response of tissues with rapid cell turnover, such as spleen, thymus, bone marrow and intestinal mucosa, they may also affect, such as suggested by some preliminary results, cancer cell proliferation and tumour growth. Therefore, further investigations are needed to understand the underlying mechanisms and to determine possible advantages and limitations of their administration to cancer patients.

Animals↗

[ Evaluation of the nutritional state of patients in emergency services: contribution in measurement of body composition].

Weight and body mass index are used in clinical routine to detect malnourished patients. However, a study performed at the emergency admission of the University Hospital of Geneva shows that the prevalence of malnutrition is very underestimated when based on body mass index instead of fat-free mass. Indeed, a third of the patients with normal body mass index, i.e. between 20 and 24.9 kg/m2, present a fat-free mass under percentile 10. This suggests that the body mass index alone cannot be used as diagnostic criteria for malnutrition. This review describes the prevalence of malnutrition at the emergency admission of the University Hospital of Geneva, the prevalence of malnutrition in the literature and its relationship with length of hospital stay and mortality.

Anthropometry↗

Body composition interpretation. Contributions of the fat-free mass index and the body fat mass index.

OBJECTIVE: Low and high body mass index (BMI) values have been shown to increase health risks and mortality and result in variations in fat-free mass (FFM) and body fat mass (BF). Currently, there are no published ranges for a fat-free mass index (FFMI; kg/m(2)), a body fat mass index (BFMI; kg/m(2)), and percentage of body fat (%BF). The purpose of this population study was to determine predicted FFMI and BFMI values in subjects with low, normal, overweight, and obese BMI. METHODS: FFM and BF were determined in 2986 healthy white men and 2649 white women, age 15 to 98 y, by a previously validated 50-kHz bioelectrical impedance analysis equation. FFMI, BFMI, and %BF were calculated. RESULTS: FFMI values were 16.7 to 19.8 kg/m(2) for men and 14.6 to 16.8 kg/m(2) for women within the normal BMI ranges. BFMI values were 1.8 to 5.2 kg/m(2) for men and 3.9 to 8.2 kg/m(2) for women within the normal BMI ranges. BFMI values were 8.3 and 11.8 kg/m(2) in men and women, respectively, for obese BMI (>30 kg/m(2)). Normal ranges for %BF were 13.4 to 21.7 and 24.6 to 33.2 for men and women, respectively. CONCLUSION: BMI alone cannot provide information about the respective contribution of FFM or fat mass to body weight. This study presents FFMI and BFMI values that correspond to low, normal, overweight, and obese BMIs. FFMI and BFMI provide information about body compartments, regardless of height.

Adipose Tissue↗