Recomendaciones sobre el uso de fórmulas para el tratamiento y prevención de las reacciones adversas a proteínas de leche de vaca / Recommendations on the use of formulas in the treatment and prevention of adverse reactions to cow's proteins

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Morphological and physiological changes during growth: an update.

Skeletal growth and changes in body composition during growth present important variations; body mass index and lean body mass related to age show important gender differences. The process of ossification is developed in two different ways, endochondral and intramembraneous. The former is characterised by the formation of bone from growth cartilage. Intramembraneous ossification is characterised by the formation of bone from a mesenchymal structure, as occurs with the flat bones of the skull. During childhood and adolescence and up to the acquisition of adult stature, two phenomenons are produced simultaneously: the synthesis of new bone from growth cartilage due to the process of endochondral ossification, and modeling-remodeling of previously synthesized bone. Bone growth and mineralisation of its extracellular matrix are simultaneous phenomenons, the final result being the acquisition and maintenance of body bone mass. A positive calcium balance is necessary during adolescence in order to achieve the maximum peak of bone mass and even with the termination of longitudinal growth of bone, the process of mineralisation can last a further 4 years. Childhood and adolescence are the period of life in which the peak of bone mass must be achieved, and if during this time this does not happen there will be a greater risk for the later development of osteoporosis. Regulation of bone mass is a polygenic process and during recent years studies have been centred on the receptor genes of vitamin D and estrogens. A maximum calcium retention during adolescence may influence the achievement of a high peak of bone mass but at a certain level of calcium intake the calcium retention reaches a plateau. The expression of grams of hydroxyapatite per square centimetre has been used clinically, or expressed in volume as g/cm3. From birth until 3 years, the increase represents approximately 30% of the total increase, from 3 years until the beginning of pubertal development the increase is 20%. During pubertal development there is an increase of 30-40% and from the end of growth until the age of 21 years there is an increase of 15-20%. Both prepubertal boys and girls show a progressive increase of leptin levels during the years prior to the onset of puberty and until Tanner's stage 11 and higher levels are observed in girls in this period, possibly in relation to their earlier onset of puberty. This increase of leptin in girls during pubertal development suggests that leptin may be a link between adipose tissue and puberty.

[A controlled, double-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury]. / Ensayo clínico piloto, controlado, doblemente ciego, aleatorizado de nicardipino frente a placebo en pacientes afectados de traumatismo craneal grave o moderado.

INTRODUCTION: One of the factors involved in the occurrence of ischemic cerebral lesions following head injury is cerebral vasospasm. We analyze the effect of intravenous nicardipine on the prevention and treatment of posttraumatic cerebral vasospasm. PATIENTS AND METHODS: We made a placebo-controlled, randomised, double-blind pilot study of the effect of nicardipine (intravenously 5 mg/hour for one week) on patients with moderate or severe head injury who presented with cerebral vasospasm, defined as an average Doppler flow velocity (DFV) of 100 cm/second or more. The main variable assessed was the evolution of the DFV and the secondary criteria were the evolution of the arterial blood pressure, coma scales, the findings on the Glasgow Coma Scale and the safety of the drug. RESULTS: Eleven patients were included in each homogeneous group. The DFV was found to have become normal on the first day of treatment with nicardipine and on the third day with the placebo (p = 0.023). During the first day of treatment the percentage of cerebral hemispheres diagnosed as having suspected spasm was 11.1% for nicardipine and 64.3% for the placebo (p = 0.02881). The average time for recovery (DFV < 100 cm/second) was 3.33 days with the placebo and 1.22 days with nicardipine (p = 0.0039). The patients treated with nicardipine had 8.89 times more chance of recovery from vasospasm. The incidence of adverse effects was greater with the placebo (p = 0.014). CONCLUSION: Nicardipine is effective in the reversal and prevention of increased Doppler flow velocity in patients with moderate or severe head injury.

Ensayo clínico piloto, controlado, doblemente ciego, aleatorizado de nicardipino frente a placebo en pacientes afectados de traumatismo craneal grave o moderado / A controlled, doublé-blind, randomized pilot clinical trial of nicardipine as compared with a placebo in patients with moderate or severe head injury

Introducción y objetivo. Uno de los factores implicados en la aparición de lesiones isquémicas cerebrales tras un traumatismo craneal es el vasoespasmo cerebral. Se analiza el efecto de nicardipino iv en la prevención y tratamiento del vasoespasmo cerebral postraumático. Pacientes y métodos. Se trata de un estudio piloto, doblemente ciego, aleatorizado y controlado por placebo, del efecto de nicardipino (5 mg/h, durante una semana, iv) en pacientes con traumatismo craneal grave o moderado que presentan vasoespasmo cerebral, definido por una velocidad media Doppler de flujo (DFV) superior o igual a 100 cm/s. La variable principal de valoración fue la evolución de las DFV y las criterios secundarios fueron la evolución de la presión arterial, las escalas de coma y de resultados en la escala de Glasgow y la seguridad del fármaco. Resultados. Se incluyeron 11 pacientes en cada grupo homogéneo. Se observó la normalización de las DFV con nicardipino en el primer día de tratamiento y con placebo, al tercer día (p= 0,023). Durante el primer día de tratamiento el porcentaje de hemisferios con el diagnóstico de sospecha de espasmo fue del 11,1% para nicardipino y del 64,3% para placebo (p= 0,02881). El tiempo medio para la recuperación (DFV <100 cm/s) es de 3,33 días para placebo y de 1,22 días para nicardipino (p= 0,0039). Los pacientes tratados con nicardipino tuvieron una posibilidad de recuperación del vasoespasmo 8,89 veces superior. La incidencia de efectos adversos fue superior con placebo (p= 0,014). Conclusión. El nicardipino es eficaz en revertir y prevenir las velocidades Doppler elevadas en pacientes con traumatismo craneoencefálico moderado o grave (AU)

Introduction. One of the factors involved in the occurrence of ischemic cerebral lesions following head injury is cerebral vasospasm. We analyze the effect of intravenous nicardipine on the prevention and treatment of posttraumatic cerebral vasospasm. Patients and methods. We made a placebo-controlled, randomised, double-blind pilot study of the effect of nicardipine (intravenously 5 mg/hour for one week) on patients with moderate or severe head injury who presented with cerebral vasospasm, defined as an average Doppler flow velocity (DFV) of 100 cm/second or more. The main variable assessed was the evolution of the DFV and the secondary criteria were the evolution of the arterial blood pressure, coma scales, the findings on the Glasgow Coma Scale and the safety of the drug. Results. Eleven patients were included in each homogeneous group. The DFV was found to have become normal on the first day of treatment with nicardipine and on the third day with the placebo (p= 0.023). During the first day of treatment the percentage of cerebral hemispheres diagnosed as having suspected spasm was 11.1% for nicardipine and 64.3% for the placebo (p= 0.02881). The average time for recovery (DFV< 100 cm/second) was 3.33 days with the placebo and 1.22 days with nicardipine (p= 0.0039). The patients treated with nicardipine had 8.89 times more chance of recovery from vasospasm. The incidence of adverse effects was greater with the placebo (p= 0.014). Conclusion. Nicardipine is effective in the reversal and prevention of increased Doppler flow velocity in patients with moderate or severe head injury (AU)

Lead exposure in children: levels in blood, prevalence of intoxication and related factors.

Lead is a highly toxic metal, the main source of which is contamination from combustion of unleaded petrol. The aims of this work were to detect the degree of lead exposure in a large sample of children; determine the relationship between blood lead levels (BPb) and age, sex, habitat and season of the year; and correlate BPb with zinc protoporphyrin (ZPP) values. A cross-sectional study was carried out. Blood from routine extractions drawn at our centre was used. BPb and ZPP were measured by atomic absorption spectrophotometry and haematofluorimetry, respectively. We analysed 1158 blood samples from children. BPb (mean +/- SEM): 0.22 +/- 0.04 mumol l-1. Correlation BPb-age: BPb = 0.19 + 0.086 x age (months), r = 0.129, P < 0.0001. BPb was greater in boys (0.23 +/- 0.007 versus 0.20 +/- 0.006 mumol l-1, P < 0.0002). No differences were observed between habitats (urban versus rural). BPb were higher in the warm months (0.24 +/- 0.013 versus 0.21 +/- 0.007 mumol l-1, P < 0.0001). Prevalence of lead intoxication (BPb > 0.48 mumol l-1) was 4.2%. No differences in prevalence were found among the different groups. The correlation between BPb and ZPP showed r = 0.0969, P = 0.0024. Utility for screening: sensitivity of 53.7% and specificity of 59.3% (cut-off point of 60 mumol ZPP mol-1 haem). We can conclude that lead exposure in children in our sample was in the range reported in similar studies in other areas and countries, and below the toxic limit. None of the factors analysed significantly influenced lead intoxication prevalence. There was no good correlation between ZPP and BPb in our samples and the ZPP cut-off point used did not present good specificity and sensitivity values.

Lead exposure in the general population of the Metropolitan Area of Barcelona: blood levels and related factors.

A cross-sectional study was conducted on 254 individuals not occupationally exposed to lead to determine the degree of lead exposure in the general population of the Metropolitan Area of Barcelona. Blood lead levels (BPb) were analysed by atomic absorption spectrophotometry and zinc protoporphyrin (ZPP) by haemofluorimetry. Blood lead levels were analysed with respect to individuals' age, sex, area of residence, the season of the year the blood was drawn and ZPP. Mean blood lead in our series was 0.22 +/- 0.011 mumol/l (mean +/- S.E.); no significant differences were found with respect to area of residence, sex or season. A linear relationship was observed between BPb and individuals' age (BPb = 0.08 + 0.05 x age; r = 0.37). The prevalence of lead intoxication (BPb > 0.48 mumol/l) was 7.1%. No linear relationship was observed between BPb and ZPP. ZPP determination does not appear to be a good screening method for lead intoxication since it presents low specificity and sensitivity values with an area below the ROC curve similar to the null value line (area below the curve = 0.5052, IC 95% = 0.443-0.568). We conclude that lead exposure does not constitute a serious health problem in the area studied, since BPb levels found are far below the toxic limit and the prevalence of intoxication is similar to that reported in other studies conducted in other developed countries.

Effect of aluminum and lead salts on lipid peroxidation and cell survival in human skin fibroblasts.

The aim of this study was to see whether aluminum (Al) and lead (Pb) salts are toxic for cultured human fibroblasts under different experimental conditions, in the controllable situation offered by cell cultures. Cell survival and membrane lipid peroxidation served as markers of Al and Pb toxicity. Evaluation of the living cells was carried out using a colorimetric method, the mitochondrial reduction of 1-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). Lipoperoxidation assay was performed on whole cell homogenates by measuring thiobarbituric acid-reactive substances (TBARS) produced after incubation with ascorbic acid-ferrous sulfate. Al(III) and Pb(II) salts (300 microM) produce a considerable decrease in cell survival after an exposure period of 4d, evident with the three fetal calf serum concentrations in the culture media: 2, 5, and 10%. Taking into account in vitro cell aging, the cytotoxic effects of Al(III) and Pb(II) are greater in senescent fibroblasts than in young cells. Lead-induced cytotoxicity is higher than Al-induced cytotoxicity. A mechanism that contributes to cellular toxicity is membrane lipid peroxidation; our results demonstrate that Al(III) and Pb(II) ions, 400 microM, exert an antioxidant-like effect or a pro-oxidant action on cell membranes depending on exposure time. We describe significant increases in TBARS formation associated with the presence of 400 microM Al(III) or Pb(II) salts in the culture media. Our study also revealed that these heavy metals induce a cell age-dependent action on membrane lipoperoxidation that is greater in senescent fibroblasts and this could have severe consequences for maintenance of cellular integrity.

Blood polyunsaturated fatty acids in patients with peroxisomal disorders. A multicenter study.

The purpose of the study was to compare the polyunsaturated fatty acid (PUFA) status in patients with X-linked adrenoleukodystrophy or adrenomyeloneuropathy (X-ALD/AMN) with that in disorders of peroxisome biogenesis (PB). Total fatty acids and plasmalogens were quantified in plasma and red cells from 28 patients with X-ALD/AMN, 26 patients with generalized peroxisomal disorders, and 37 controls. Total fatty acid methyl esters and plasmalogen dimethyl acetals were obtained by direct transmethylation and separated by capillary column gas chromatography. The results confirm previous findings in that docosahexaenoic acid (DHA, 22:6n-3) was greatly decreased in both plasma and erythrocytes from patients with PB disorders. When nutritional conditions were adequate, patients with X-ALD/AMN had normal levels of DHA. A highly significant positive correlation was found between the levels of DHA and those of plasmalogens in peroxisomal patients. As in other tissues, the parent n-6 fatty acid, linoleic acid (LA, 18:2n-6) was significantly increased in red cells from PB patients, whereas arachidonic acid (20:4n-6) was virtually within normal limits. In clear contrast to red cells and other tissues, arachidonate was significantly lower in plasma from PB patients. The decrease in plasma arachidonate and the high tissue levels of LA suggest a defect of delta 6 desaturase and/or delta 5 desaturase in PB patients. The n-6 fatty acids were normal in X-ALD/AMN patients. The present data show that X-ALD/AMN patients do not have the profound PUFA alterations that PB patients have, at least in blood.

Aluminum in the neonate related to parenteral nutrition.

Sources of aluminium loading and exposure in preterm and full-term newborns were studied. Parenteral nutrition solutions were the main source of aluminium representing 88.7% of total aluminium intake. Blood and urine aluminium levels were followed over a 28-day period in a group of 26 preterm and 9 term infants while receiving parenteral nutrition (duration 15.6 +/- 8.7 days) and later when being formula fed. Urine levels were followed up to 13 weeks in a subgroup of the neonates. Serum aluminium levels (0.86 +/- 0.38 mumol/l) and urine aluminium/creatinine ratio (1.52 +/- 0.81 mumol/mmol) were increased when the infants were receiving parenteral nutrition compared with the control group (p < 0.001). The urine aluminium/creatinine ratio remained high up to 10 weeks following withdrawal of parenteral nutrition and suggested tissular loading. This was confirmed after high aluminium levels were found in post-mortem brain and bone samples from two preterm and one full-term infant. We conclude that both preterm and full-term neonates are susceptible to accumulation of aluminium in tissue while receiving parenteral nutrition.

Somatostatin effects on cultured human fetal epiphyseal chondrocytes.

Somatostatin effects on cultured human fetal epiphyseal chondrocytes were evaluated by studying the effects of somatostatin on DNA synthesis. Cultured epiphyseal chondrocytes from human fetuses (12-40 wk old) were incubated for 48 h in Ham's F-12 serum-free medium. After this, the medium was replaced by MCDB-104 serum-free medium and the cells were incubated for an additional 48 h in the presence or absence of somatostatin 1 pM to 10 microM, with the addition of 3H-thymidine (5 microCi/mL) for the last 24 h of incubation. A significant (p < 0.02) inhibitory effect of somatostatin (1 nM to 10 microM) on 3H-thymidine DNA incorporation was observed in cultured chondrocytes from fetuses of all gestational ages studied (12-40 wk), with no significant differences among fetal ages. In conclusion, our results show that somatostatin exerts a biologic effect on cultured human fetal epiphyseal chondrocytes, as it does in its target cells. These results suggest that somatostatin could regulate human skeletal growth not only by growth hormone secretion regulation, but also by acting directly on chondrocyte metabolism. However, the physiologic significance of the latter remains to be elucidated.

Effects of triiodothyronine (T3) and identification of specific nuclear T3-binding sites in cultured human fetal epiphyseal chondrocytes.

The effects of T3 on cultured human fetal epiphyseal chondrocytes were assessed by studying its effects on DNA synthesis and alkaline phosphatase activity. DNA synthesis was evaluated as follows: after 48-h incubation in Ham's F-12 serum-free medium, cultured chondrocytes were incubated with or without T3 (0.1-100 nM) in MCDB-104 serum-free medium for different periods of time (2-10 days), with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. Confluent cultured chondrocytes in 25-cm2 tissue culture flasks were incubated in Ham's F-12 serum-free medium for up to 9 days with or without T3 (0.1-100 nM); the cellular cytoplasmic fraction was obtained, and alkaline phosphatase activity was evaluated using paranitrophenylphosphate as a substrate. No significant effects of T3 (0.1-100 nM) on DNA-[3H]thymidine incorporation were observed in any experiment (n = 17) for any gestational age (12-39 weeks) or for any incubation period studied (2-10 days). However, a significant (P less than 0.025 or more) stimulatory effect of T3 (0.1-100 nM) on alkaline phosphatase activity was observed after 9 days of incubation. This effect was highest for 5 nM T3 and was present in cultured chondrocytes from human fetuses of all ages studied (13-40 weeks). Cultured human fetal epiphyseal chondrocytes from human fetuses 12-40 weeks old (n = 8) showed specific nuclear binding sites for T3. The binding capacity was 27.14 +/- 2.84 fmol/100 micrograms DNA, and the Kd was 0.66 +/- 0.14 x 0.1 nM (mean +/- SEM), with no significant differences among fetal ages. In conclusion, our results show that T3 elicits a biological response in cultured human fetal epiphyseal chondrocytes and has specific nuclear binding sites. Since alkaline phosphatase is closely related to the mineralization of epiphyseal cartilage, these results suggest that thyroid hormones could regulate this process.