Musical and psychomotor interventions for cognitive, sensorimotor, and cerebral decline in patients with Mild Cognitive Impairment (COPE): a study protocol for a multicentric randomized controlled study.

BACKGROUND: Regular cognitive training can boost or maintain cognitive and brain functions known to decline with age. Most studies administered such cognitive training on a computer and in a lab setting. However, everyday life activities, like musical practice or physical exercise that are complex and variable, might be more successful at inducing transfer effects to different cognitive domains and maintaining motivation. "Body-mind exercises", like Tai Chi or psychomotor exercise, may also positively affect cognitive functioning in the elderly. We will compare the influence of active music practice and psychomotor training over 6 months in Mild Cognitive Impairment patients from university hospital memory clinics on cognitive and sensorimotor performance and brain plasticity. The acronym of the study is COPE (Countervail cOgnitive imPairmEnt), illustrating the aim of the study: learning to better "cope" with cognitive decline. METHODS: We aim to conduct a randomized controlled multicenter intervention study on 32 Mild Cognitive Impairment (MCI) patients (60-80 years), divided over 2 experimental groups: 1) Music practice; 2) Psychomotor treatment. Controls will consist of a passive test-retest group of 16 age, gender and education level matched healthy volunteers. The training regimens take place twice a week for 45 min over 6 months in small groups, provided by professionals, and patients should exercise daily at home. Data collection takes place at baseline (before the interventions), 3, and 6 months after training onset, on cognitive and sensorimotor capacities, subjective well-being, daily living activities, and via functional and structural neuroimaging. Considering the current constraints of the COVID-19 pandemic, recruitment and data collection takes place in 3 waves. DISCUSSION: We will investigate whether musical practice contrasted to psychomotor exercise in small groups can improve cognitive, sensorimotor and brain functioning in MCI patients, and therefore provoke specific benefits for their daily life functioning and well-being. TRIAL REGISTRATION: The full protocol was approved by the Commission cantonale d'éthique de la recherche sur l'être humain de Genève (CCER, no. 2020-00510) on 04.05.2020, and an amendment by the CCER and the Commission cantonale d'éthique de la recherche sur l'être humain de Vaud (CER-VD) on 03.08.2021. The protocol was registered at clinicaltrials.gov (20.09.2020, no. NCT04546451).

[Feto-maternal metabolism in human normal pregnancies: study of 73 cases]. / Métabolisme foeto-maternel au cours de grossesses humaines normales: étude de 73 cas.

From 73 normal pregnancies of gestational age between 17 and 41 weeks of gestation (WG), the concentrations of glucose, pyruvate and lactate, free fatty acids, ketone bodies (aceto-acetate and beta-hydroxybutyrate) and cholesterol were assessed on maternal venous blood (MVB) and umbilical venous blood (UVB), sampled by cordocentesis. The objective of this work was to study feto-maternal metabolism, as well as nutritional exchange between maternal blood and fetal blood during the second and third trimesters of pregnancy. Maternal and fetal glycemias, as well as maternal-fetal glucose concentration gradient, were found stable during the studied gestational period; maternal glucose is always higher than fetal glucose, with a mean concentration delta of 0.69+/-0.34 mmol/L. Maternal lactate level (1.26+/-0.38 mmol/L) is lower than fetal lactate level (1.48+/-0.46 mmol/L), whereas maternal blood pyruvate concentration (0.042+/-0.020 mmol/L) is higher than fetal blood pyruvate concentration (0.025+/-0.010 mmol/L). Consequently, mean lactate / pyruvate ratio is found twice lower in maternal blood (31.77+/-9.89) than in fetal blood (64.10+/-17.12). Free fatty acids concentration is approximately three times higher in maternal blood than in fetal blood (respectively 0.435+/-0.247 mmol/L and 0.125+/-0.046 mmol/L). Maternal venous aceto-acetate (0.051+/-0.042 mmol/L) and beta-hydroxybutyrate (0.232+/-0.270 mmol/L) concentrations are significantly lower than those in UVB (respectively 0.111+/-0.058 and 0.324+/-0.246 mmol/L) and the beta-hydroxybutyrate/aceto-acetate ratio is on average 1.7 times higher in MVB (4.75+/-2.5) than in UVB (2.82+/-1.18). Cholesterol concentration is significantly higher in maternal blood (6.26+/-1.40 mmol/L) than in fetal blood (1.66+/-0.34 mmol/L). Our results show the characteristics of oxidative metabolism of the fetus compared with that of the adult. Blood concentration in energy substrates, measured with glucose and free fatty acids levels, is low in UVB and suggests increased energy needs of the growing fetus. Mean high concentrations in aceto-acetate and beta-hydroxybutyrate in UVB, indicate probably fetal ketogenesis. UVB low cholesterolemia suggests high cholesterol consumption in the fetal compartment for cellular membrane synthesis and steroid biosynthesis.

[Biochemical profile of fetal blood sampled by cordocentesis in 35 pregnancies complicated by growth retardation]. / Etude biochimique du sang foetal prélevé par cordocentèse au cours de 35 grossesses compliquées de retard de croissance.

AIM OF THE STUDY: Intra-uterine growth retardation (IUGR) is a frequent pathology in obstetrics characterized by high heterogeneity. Fetal smallness is sometimes constitutional, but can also be accompanied by fetal distress and vital risks for the infant. In 35 pregnancies complicated by IUGR of different etiologies, we measured on fetal blood obtained by cordocentesis, biochemical variables characteristic of the fetuses' respiratory and metabolic status. The aim of the study was to identify the discriminative biological alterations, related to growth retardation and fetal distress. PATIENTS AND METHODS: The studied population includes 27 cases of severe IUGR, of gestational age 30,2+/-4,6 weeks of gestation (WG) (divided into 20 cases of isolated IUGR and 7 cases of IUGR associated with malformative syndrome), as well as 8 cases of moderate IUGR, of gestational age 26+/-4,5 WG; all fetuses had normal karyotypes. A group of 73 normal fetuses, of gestational age 26,3+/-5,7 WG, constituted a reference population. PH, pCO(2), bicarbonate concentration, pO(2) and SaO(2), as well as glucose, pyruvate, lactate, free fatty acids, aceto-acetate, beta-hydroxybutyrate and cholesterol concentrations were measured on umbilical venous blood (UVB). RESULTS: In case of severe but isolated growth retardation, UVB analysis showed the frequency of acid-base and gasometric disturbances: acidemia and hypoxemia (65% of cases), hypercapnia (60% of cases). Metabolic abnormalities were shown: decrease in glycemia (35% of cases), increase in pyruvatemia and lactatemia (40% of cases), increased free fatty acids serum concentration; a diminution of umbilical venous cholesterol level, the most frequent abnormality, can be seen in 70% of fetuses. In case of severe IUGR associated with malformative syndrome, UVB acid-base and metabolic changes were rarely seen; however, UVB cholesterol level is low in some cases. In case of growth retardation classified as moderate, modifications are relatively not frequent and essentially gasometric. CONCLUSION: In about 60% of cases of severe and isolated IUGR, there is a risk of fetal distress, related to an alteration of the transplacental transfer of respiratory gases and nutritional substrates; chronic fetal malnutrition can be involved, with an impact on the growth of the fetus. In case of IUGR associated with malformative syndrome, fetal smallness is probably a result of intrinsic fetal damage, without nutritional origin.

Molecular analysis of SRY gene in patients with mixed gonadal dysgenesis.

Mixed gonadal dysgenesis (MGD) includes a group of heterogeneous conditions consisting of a dysgenetic testis with a streak gonad. MGD is probably due to a disturbance in testicular determination/differentiation. The objective of this study is to analyze the SRY gene in MGD patients. A molecular investigation was undertaken in sixteen patients with this disorder in an attempt to determine mutations in SRY through polymerase chain reaction, single strand conformational polymorphism and direct sequencing. Eleven patients showed 45,X/46,XY and five 46,XY karyotype. Mutations in SRY gene were shown to be absent in these patients. This study confirms the findings of other studies. The etiology of MGD is heterogeneous, and cytogenetics mosaicism typically seen in these patients may be a cause of this condition, although, the presence of mutations in testicular organizing genes downstream of SRY is still to rule out.

[Arachidonate to saturated fatty acid ratio of circulating sterides and phospholipids: can it be risk marker of coronary stenosis? A Tunisian study]. / Le rapport arachidonate sur acides gras saturés des stérides et des phospholipides circulants: peut-il être un témon du risque de sténose coronarienne? Etude dans une population tunisienne.

The prevention and early diagnosis of cardiovascular diseases is a public health priority in Tunisia and actions are undertaken to evaluate biologic marquers in at risk populations. Concentrations of fatty acids in serum phospholipids and sterides have been measured using thin layer chromatography and gaz chromatography of transmethyled derivatives. The study concerned 98 coronarographed patients, presenting (n = 72) or not coronary artery disease (n = 26). The results have been compared to those of a reference population (n = 43) without any cardiac pathology. The mean concentrations of most of sterides fatty acids in coronarographed patients were higher than in controls, except for arachidonic acid which was slightly lower (68 +/- 34 mg/L versus 77 +/- 19,6 mg/L in controls). Considering concentrations of sterides fatty acids in the two subgroups of patients, coronary artery disease was associated with an increase of all these fatty acids, which was statistically significant for palmitate, linoleate and linolenate. Measurements of fatty acids in phospholipids showed a reduction of arachidonic acid in coronarographed patients (76 +/- 36,7 mg/L versus 135 +/- 49,3 mg/L in controls), but without correlation with the severity of the stenosis.

Fibroblast growth factor receptor 1 (FGFR1) is over-expressed in benign prostatic hyperplasia whereas FGFR2-IIIc and FGFR3 are not.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the major public health problems among men: 50% of men over 55 are concerned with this disease. Prostate growth is under the control of androgens which act by means of several growth factors such as fibroblast growth factors (FGFs), epidermal growth factor and transforming growth factor beta. Basic FGF (bFGF) has been shown to stimulate prostatic stromal growth. In BPH, bFGF concentration is two- to threefold higher than in normal prostate. In this work, the bFGF receptors (FGFR1, FGFR2-IIIc and FGFR3) genes expression was evaluated to study the correlation between the expression of bFGF receptors and induction of BPH. METHODS: The expression of FGFRs was analyzed by RT-PCR, FGFR1 was localized by immunohistochemistry and protein expression was evaluated by Western blot. RESULTS: A two- to eightfold over-expression of FGFR1 was observed in BPH compared with normal prostates. FGFR1 was localized in the stroma both in BPH and in normal prostates and 1.5- to 2.5-fold over-expression of the protein was observed. The expression of FGFR2-IIIc and FGFR3, more secondary receptors, was not significantly different between BPH and normal prostates. CONCLUSIONS: bFGF receptors and particularly FGFR1 seem to be involved in the induction and evolution of BPH and probably potentiate bFGF over-expression effects in BPH.

Oxidants and antioxidants in long-term haemodialysis patients.

Survival for decades is now possible in end-stage renal disease patients (ESRD) treated with haemodialysis (HD). Long-term survivors may present dialysis-related pathology (DRP). Alterations in lipid metabolism and oxidative stress are recognized as important risk factors that could be prevented or reduced by optimal therapy. We have studied markers of oxidative stress in patients receiving HD treatment for more than 20 years. In order to evaluate a preventive intervention against oxidative damage we measured the factors implied for the prooxidative and antioxidative mechanisms in haemodialysis patients. Ten long-term HD survivors (HD duration: 274.2 months) and ten patients with recent onset of HD (HD duration: 17.8 months), had blood drawn for plasma vitamins A and E, malondialdehyde (MDA), plasma and RBC glutathione peroxidase (GPx), RBC superoxide dismutase (SOD), plasma and erythrocyte glutathione reductase (GSSG-R), oxidized and reduced glutathione (GSH) assessment. Despite normal levels of antioxidant vitamins, an usual finding in this setting, increased MDA, and oxidized GSH, and decreased plasma GPx and reduced GSH show that oxidant stress is markedly present in both recent onset and long-term HD patients. It would appear highly advantageous to reduce complications of long-term dialysis patients with preventing modalities.

Basic fibroblast growth factor and keratinocyte growth factor over-expression in benign prostatic hyperplasia.

The prostate growth is under the indirect control of androgens through the medium of many growth factors. The fibroblast growth factors (FGFs) seem to play an important part in stimulating the development of this organ. In this work, the expression of two FGFs: bFGF (or FGF2) and KGF (or FGF7), was studied in RT-PCR and semi-quantified in densitometry. Both genes expression was increased in BPH in comparison with normal prostates. A two to three times and a 1.5 to four times over-expressions were observed for bFGF and KGF, respectively. An over-expression of these growth factors could lead to a cell multiplication resulting in a pathological development of the prostate size. Moreover, bFGF and KGF act in parallel in the prostate, one stimulating the prostatic stroma and the other one stimulating the epithelium. These two growth factors could participate in the increase of the two tissues constituting the prostate.

Low-density lipoprotein (LDL) behavior after in vitro oxidation in three groups of diabetics.

Diabetes is associated with increased morbidity and mortality resulting from cardiovascular disease. It has been established that oxidized LDLs are involved in the genesis of atherosclerosis. We have studied LDL oxidizability in three types of diabetics: insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-treated diabetes mellitus type 2 (ITDM2) and a control group. LDLs have been isolated using ultracentrifugation and oxidized by addition of cupric chloride. With the oxidation kinetic, we calculated the lag time and the oxidation rate. Total fatty acids, alpha-tocopherol, and malondialdehyde (MDA) have been measured in native and oxidized LDLs. Diabetics have a significantly lower lag time and a lower level of alpha-tocopherol. Oxidized LDLs of diabetics show an important decrease of their polyunsaturated fatty acids with an increase of MDA compared to the control. Our study demonstrates a higher susceptibility to oxidation of LDL from diabetics; this can be explained by alteration in LDL composition or by the oxidative process occurring in this disease.

Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death.

The toxic effect of thiram, a widely used dithiocarbamate fungicide, was investigated in cultured human skin fibroblasts. Cell survival assays demonstrated that thiram induced a dose-dependent decrease in the viable cell recovery. Thiram exposure resulted in a rapid depletion of intracellular reduced glutathione (GSH) content with a concomitant increase in oxidized glutathione (GSSG) concentration. Alteration of glutathione levels was accompanied by a dose-dependent decrease in the activity of glutathione reductase (GR), a key enzyme for the regeneration of GSH from GSSG. Thiram-exposed cells exhibited increased lipid peroxidation reflected by enhanced thiobarbituric acid reactive substances (TBARS) production, suggesting that GSH depletion and the lower GR activity gave rise to increased oxidative processes. To investigate the role of decreased GSH content in the toxicity of thiram, GSH levels were modulated prior to exposure. Pretreatment of fibroblasts with N-acetyl-L-cysteine (NAC), a GSH biosynthesis precursor, prevented both lipid peroxidation and cell death induced by thiram exposure. In contrast, thiram cytotoxicity was exacerbated by the previous depletion of cellular GSH by L-buthionine-(S,R)-sulfoximine (BSO). Taken together, these results strongly suggest that thiram induces GSH depletion, leading to oxidative stress and finally cell death.

Evaluation of the rennin-angiotensin-aldosterone system in hypertensive Ivoirian subjects--preliminary results.

Experimental data on the renin-angiotensin-aldosterone system in black Africans are very limited. In this study we set up our own values (plasma renin and aldosterone) in a group of normotensive Ivoirian male and female (N = 43) subjects and compared our results with those published for the white population. The values were approximately the same. A parallel study was carried out in a black population (N = 48 men and women) consulting a doctor for the first time for hypertension in different regions of Côte d'Ivoire. The mean values of plasma renin and aldosterone were significantly higher (P < 0.05) in the hypertensive compared with the control group.

An evaluation of thiram toxicity on cultured human skin fibroblasts.

Thiram is widely used in agriculture as a fungicide and, to a lesser extent, as a vulcanizing agent in the rubber industry. In spite of the extensive use of thiram, knowledge on its toxicity and health risk remains limited, and few investigations have been performed to assess specific damage at the cellular and subcellular level. We report here the cytotoxic effects of thiram on cultured human skin fibroblasts. Our results demonstrated that thiram exposure induced a dose- and time-dependent decrease in the viable cell recovery with 100% cell death observed with a concentration of 5.0 mg/l. As judged by morphological changes and biochemical criteria, thiram-mediated cell death was not of the apoptotic but seemed to be of the necrotic type. This cell death was not associated with a modification of gene expression of different constituents of the extracellular matrix. A late increase of lactate production was evident after thiram treatment, suggesting a mitochondrial metabolic pathway dysfunction as reported by other authors using similar compounds. However, this phenomenon appeared as a secondary response to the toxic action of thiram. The cytotoxic effect of thiram is possibly due to an oxidant effect inherent to the structure of thiram and the interaction between thiram and vital cellular molecules.

Quantitation of reduced and total glutathione at the femtomole level by high-performance liquid chromatography with fluorescence detection: application to red blood cells and cultured fibroblasts.

A new rapid and highly sensitive HPLC method with ortho-phthalaldehyde (OPA) pre-column derivatization has been developed for determination of reduced glutathione (GSH) and total glutathione (GSHt) in human red blood cells and cultured fibroblasts. OPA derivatives are separated on a reversed-phase HPLC column with an acetonitrile-sodium acetate gradient system and detected fluorimetrically. An internal standard (glutathione ethyl ester) is added to facilitate quantitation. Total glutathione is determined after reduction of disulfide groups with dithiothreitol; the oxidized glutathione (GSSG) concentration is calculated by subtraction of the GSH level from the GSHt level. The assay shows high sensitivity (50 fmol per injection, the lowest reported), good precision (C.V. <5.0%), an analytical recovery of GSH and GSSG close to 100%, and linearity (r > 0.999). This HPLC technique is very simple and rapid. Its wide applicability and high sensitivity make it a convenient and reliable method for glutathione determination in various biological samples.

Severe hypertriglyceridaemia in Type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is common in Type II (non-insulin-dependent) diabetes mellitus. Only subgroups of patient however have type V hyperlipidaemia. To investigate the coordination between genetic factors in the modulation of hypertriglyceridaemia in Type II diabetes, we studied three major modifier loci: apoC-III (both Sst-I and insulin-responsive element polymorphisms), apolipoprotein E genotypes and lipoprotein-lipase mutations. METHODS: We studied apoCIII gene polymorphisms, apolipoprotein E genotypes and lipoprotein-lipase gene mutations in 176 patients with Type II (non-insulin-dependent) diabetes mellitus, either normolipaemic (group N, n = 116), mildly hypertriglyceridaemic (group T, n = 28) or with a history of severe hypertriglyceridaemia (triglyceride > 15 g/l) (group H, n = 32). RESULTS: Mild hypertriglyceridaemia in Type II diabetes did not associate with any gene variants in this study. Severe hypertriglyceridaemia was, however, associated with the presence of the apoC-III S2 allele (50% of the patients in group H compared with 15.5 % in group N, p < 0.0001). Additionally this particular phenotype was associated with a low prevalence of the apo E3 allele (35.9% in group H vs 18.1 % in group N, p < 0.005) and a statistically significant over-representation of the E2E4 genotypes. Inactivating lipoprotein-lipase mutations were found in four patients (three heterozygotes, one homozygote), none was found in group N or T. Thus 68.7 % of group H patients (22/32) (vs 21.4 % in group T, p < 0.0005) were carriers of either S2 allele, lipoprotein-lipase mutants or E2E4 genotype with most lipoprotein-lipase mutants or E2E4 genotypes or both in the non-carriers for the S2 allele (6/7). CONCLUSION/INTERPRETATION: Our results strongly support the hypothesis that severe hyperlipaemia in Type II diabetes crucially depends on genetic factors which impair the clearance of triglyceride-rich lipoproteins.

Lipid peroxidation and antioxidant defenses in cystic fibrosis patients.

Lipid peroxidation biomarkers and antioxidant status were measured in 76 cystic fibrosis (CF) patients and compared to 40 control subjects. Univariate and multivariate statistics were performed in this study. Results showed that indicators of lipid peroxidation were higher in CF patients than in controls; thiobarbituric acid reactants and autoantibodies against oxidized low-density lipoproteins were significantly increased in CF patients. Red blood cells and whole blood glutathione peroxidase activities were lower in CF patients than in controls. No difference in red blood cell superoxide dismutase activity was observed. Measured concentration of glutathione peroxidase in plasma showed a higher mean value of this protein in CF patients than in controls. Retinol, alpha-tocopherol and beta-carotene concentrations were all reduced in CF patients as compared to controls; this was particularly pronounced for beta-carotene. The decreased alpha-tocopherol concentration was associated with higher percent hemolysis in CF patients. The results of this study indicate that both lipid peroxidation biomarkers and antioxidant status were disturbed in CF patients, despite medical assistance. Measures of oxidative stress parameters, such as thiobarbituric acid reactants, glutathione peroxidase, and beta-carotene concentrations can be considered as significant indicators to discriminate CF patients and control subjects.

RER(+) phenotype in prostate intra-epithelial neoplasia associated with human prostate-carcinoma development.

The mutator (RER(+)) phenotype has been shown to be a mutational mechanism for tumour-suppressor-gene inactivation in colorectal cancer. A group of 60 prostate-carcinoma patients was studied to determine the frequency, intratumour distribution and timing of mutator phenotype in this cancer. Ten microsatellite loci were analyzed in 172 carcinoma foci (CF) and in 57 associated non-cancerous prostate tissues, including 31 areas of prostate intra-epithelial neoplasia (PIN) and 26 non-dysplastic areas with glandular hyperplasia (HP). We detected lesions with the RER(+) phenotype in 42% (25/60) of the prostate tumours. Clonal foci with RER(+) phenotype were detected at similar frequencies in pre-cancereous PIN (16%, 5/31) as in associated carcinoma foci (22%, 37/172), but were detected in only one of the 26 non-dysplastic prostate tissues studied (4%). Thus, clonal RER(+) foci were significantly more frequent in CF than in HP (p < 0.05). MI itself was significantly more frequent in CF (53%, p < 0.0001) and in PIN (35%, p < 0.05) than in HP (12%). Furthermore, 5 PIN harboured microsatellite mutations also detected in the associated cancer. Our overall results therefore strongly suggest that the mutator phenotype may occur as an early event in prostate tumorigenesis.

Variability of Ha-ras (codon 12) proto-oncogene mutations in diverse thyroid cancers.

Structural alterations to proto-oncogene sequences may be involved in the pathogenesis of human thyroid neoplasms. We studied 128 thyroid tumours (35 benign and 93 malignant) for ras gene point mutations in three different codons (12, 13 and 61) using a restriction fragment length polymorphism technique and direct sequencing of double-stranded DNA on polymerase chain-reaction-amplified tumour DNA. We found a high frequency of ras mutation for the Ha-ras codon 12 in follicular adenomas (7 of 35), particularly in atypical adenomas (5 of 17), in follicular carcinomas (6 of 19), with a high percentage for Hurthle cell carcinomas (6 of 11), and in papillary carcinomas (4 of 66). Point mutations for other ras genes in different codons studied were weak to absent. No mutation was found in undifferentiated carcinomas (n = 8). The predominant amino acid substitution both in the adenomas and in the differentiated tumours was glycine to valine (GGC to GTC) at position 12 of the Ha-ras gene. Our results obtained on a large series confirm the frequent occurrence of Ha-ras codon 12 gene mutations both in adenomas and in carcinomas. The frequency of ras mutations is linked to the geographical origin of the population studied and varies (0-85%) from one cancer type to another according to published data. Therefore, these mutations are merely an expression of cellular transformation.

Biochemical assessment of the nutritional status of cystic fibrosis patients treated with pancreatic enzyme extracts.

We examined the protein and fat nutritional status of 65 cystic fibrosis patients aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic enzyme extracts to improve nutrient absorption; in addition, most patients were supplemented with vitamins A and E. Results were compared with those in a control group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases or nutritional deficiencies. Protein determination showed low albumin concentrations in 42% of the cystic fibrosis patients and decreased blood concentrations of retinol binding protein in 12% of the patients. Lipoprotein components were characterized by decreased cholesterol concentrations in 25% of the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were significantly lower in the cystic fibrosis group than in control subjects. The results of fatty acid status, expressed in relative (%) and absolute (mg/L) values, showed concentrations of essential fatty acids, represented by linoleic and arachidonic acids, to be significantly decreased in cystic fibrosis patients; this decrease was markedly significant for fatty acid status expressed in absolute values, especially in the cholesteryl ester subfraction. Serum retinol and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/- 0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0 micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis patients was completely corrected.