Sobre: Niña de 10 años con infección por el nuevo virus de infl uenza A (H1N1) / About: «Infection by the new swine fl u virus A (H1N1) in a ten-year-old girl>

No disponible

No disponible

Chip-mediated techniques: how close are we to generalised use in the infectious disease clinic?

This could be the beginning of a new molecular era for the diagnosis of infectious diseases. Biological chips (biochips or microarrays and labchips) offer a potentially important shortcut to early diagnosis and treatment. It is also possible to develop multiplex assays for use in complex diagnostic situations; however, this technology depends crucially on the robotics developed to support these functions, and the soundness of the mathematics employed to analyse the output. Although the number of research applications is increasing, the question as to when, or if, chip-mediated techniques will be used routinely in the infectious disease clinic remains unanswered at present.

The effects of estrogen administration on bone mineral density in adolescents with anorexia nervosa.

OBJECTIVE: Profound osteopenia is a serious complication of anorexia nervosa (AN). The aim of this work was to study the effect of prolonged AN on lumbar spine bone mineral density (BMD) and to determine whether oral estrogen administration prevents bone loss in women with this disorder. SUBJECTS AND METHODS: Thirty-eight amenorrheic women with AN (mean age: 17.3 years) were treated with estrogen (50 microg of ethinyl estradiol) and gestagen (0.5 mg of norgestrel) during 1 year. Clinical variations, biochemical indices and BMD were studied at three different time points, including after a period of amenorrhea of at least 12 months (n=38), after the administration of estrogens for 1 year (n=22), and after a 1-year follow-up period (n=12). RESULTS: Initial mean BMD was significantly lower than normal (-2.1+/-0.8 s.d.) and less than -2.5 s.d. below normal in 38% of the women with AN. The estrogen-treated group had no significant change in BMD even after the follow-up period and partial recovery of weight. Estradiol and total IGF-I levels were significantly lower throughout the study. All subjects had normal thyroxine (T(4)) and TSH levels and calcium metabolism. However, total tri-iodothyronine (T(3)) was decreased in all anorexic subjects in the first and second study points and were within normal limits after the follow-up period. CONCLUSIONS: (1) Estrogen replacement alone cannot prevent progressive osteopenia in young women with AN. (2) Other factors, such as the loss of weight, the duration of the amenorrhea and the low levels of total insulin-like growth factor-I (IGF-I) could contribute to the loss of bone mass in women with this disorder.

[Oral drugs that should not be crushed]. / Fármacos orales que no deben ser triturados1

In patients hospitalized in intensive care units (ICUs) nasogastric tubes are used for enteral feeding and solid pharmaceutical preparations are commonly administered. These drugs must be crushed before administration, which may alter their pharmacokinetic properties and consequently their therapeutic effects and adverse reactions, etc. The aim of this study was to review the orally-administered drugs used in our unit that should not be crushed, to propose alternative measures and to make recommendations for their correct administration. Their descriptive study was performed in the ICU of a University Hospital with 12 general-purpose beds. We reviewed all the oral medication currently administered in our unit and its form of administration through the nasogastric tube. Oral pharmaceutical preparations that should not be crushed were identified through a review of articles in MEDLINE published between 1991 and 2000 and through consultations with various pharmacy departments. Alternatives to these drugs were sought. Of the 115 drugs used in our unit, 50 could not be crushed. The pharmaceutical preparation of this group of drugs should not be modified because crushing would alter their characteristics, pharmacokinetic properties, etc. We present alternatives and make recommendations for their correct administration. In conclusion, a practical guide for the administration of drugs through nasogastric tubes is required. In our unit, such a guide would increase the efficacy and safety of the pharmacological treatment administered in this way. Collaboration with the pharmacy department is also advisable.

Fármacos orales que no deben ser triturados / Oral drugs that should not be crushed

Los pacientes ingresados en cuidados críticos, son portadores de sonda nasogástrica (SNG) para la alimentación enteral y es común administrar formas farmacéuticas sólidas (FFS). Esto hace que algunos preparados farmacéuticos tengan que ser triturados para su administración, lo que puede cambiar sus propiedades farmacocinéticas y por lo tanto su efecto terapéutico, reacciones adversas, etc. El objetivo de este trabajo es revisar los fármacos que se utilizan por vía oral en nuestra Unidad que no deben ser triturados, proponer medidas alternativas y recomendaciones para una administración correcta. Este estudio descriptivo fue realizado en la Unidad de Cuidados Intensivos (UCI) de un Hospital Universitario de 12 camas polivalentes. Para llevar a cabo el trabajo revisamos toda la medicación oral que se administra actualmente en nuestra unidad y su modo de administración a través de la sonda. Mediante una revisión bibliográfica de la base de datos de Medline entre los años 1991-2000 y consultas a distintos servicios de farmacia, se identificaron las formas farmacéuticas orales (FFO) que no se deben triturar y se buscaron sus alternativas. De los 115 fármacos que se utilizan en nuestra unidad encontramos que 50 de ellos no se pueden triturar. En este grupo de fármacos no se debe modificar la forma farmacéutica (FF) del preparado, por tratarse de formas farmacéuticas cuya trituración altera sus características, propiedades farmacocinéticas, etc. Se presentan las alternativas y recomendaciones para su correcta administración. Como conclusión, es necesario la elaboración de una guía práctica de administración de medicamentos por SNG, que permitiría en nuestra unidad una mayor eficacia y seguridad del tratamiento farmacológico para esta forma de administración. En cualquier caso debe existir una colaboración con el servicio de farmacia (AU)

Insulin-like growth factor I, insulin-like growth factor binding proteins, and growth hormone binding protein in Spanish premature and full-term newborns.

The normal values of insulin-like growth factor I (IGF-I), IGF-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3), and the high-affinity growth hormone binding protein (GHBP) are not well established in large series of healthy fullterm newborns. We report the normative data for IGF-I, IGFBP-I, IGFBP-3, and GHBP in 271 normal Spanish full-term newborns, born between 37 and 42 weeks of gestation, and compare these results with the same parameters studied in 39 premature infants. Furthermore, we report the relationship between results found in the normal full-term newborns and those of 252 healthy prepubertal (Tanner stage I) Spanish children. Serum GHBP, IGF-I, and IGFBP-3 levels are very low in the premature infant and show a significant increase in full-term newborns, and continue to decline during childhood (p < 0.001; analysis of variance). A positive correlation between GHBP, IGF-I, and IGFBP-3 versus gestational age was observed. In contrast, we found a negative correlation between IGFBP-I and gestational age. There is a direct relationship between the ponderal index and IGF-I and IGFBP-3. When the group of premature newborns was divided into infants born before or after 32 weeks of gestation, we found higher levels of IGF-I and IGFBP-3 (p < 0.01 and p < 0.05, respectively, by Student's test) in the group with the higher gestational age; however, the IGFBP-I level was lower in this group (p < 0.001 by Student's t test), with no differences seen in serum GHBP concentrations. The presence of IGFBPs in the premature infant suggests that they are important modulators of IGF-I action during fetal growth and development.

Normative data for insulin-like growth factors (IGFs), IGF-binding proteins, and growth hormone-binding protein in a healthy Spanish pediatric population: age- and sex-related changes.

The normal values of insulin-like growth factors (IGFs) after extraction, their binding proteins, and the high affinity GH-binding protein are not well established in infancy or childhood. We report the relationship between serum IGF-I, IGF-II, their binding proteins IGFBP-1 and IGFBP-3, and GH-binding protein in 600 normal Spanish children who were divided into 5 groups according to Tanner stage: I, 150 males and 102 females; II, 40 males and 42 females; III, 45 males and 45 females; IV, 42 males and 55 females; and V, 23 males and 56 females. Serum IGF-I levels increase slowly during childhood in both sexes, exhibiting a dramatic increase during puberty and a significant decline [P < 0.001, by analysis of variance (ANOVA)] during adulthood. The pubertal peak occurs approximately 2 yr earlier in girls than in boys. In contrast, serum IGF-II levels remain stable throughout childhood, showing no pubertal peak. In boys, there is a significant decline in IGF-II levels during adulthood (P < 0.001). Serum IGFBP-3 levels show a pattern similar to that of IGF-I, with a significant increase during childhood and a significant decline during adulthood (P < 0.001, ANOVA) in both males and females. In contrast, serum IGFBP-1 levels decrease dramatically during childhood in both boys and girls (P < 0.001 and P < 0.005, respectively, by ANOVA). A significant decline in serum GH-binding protein levels is observed between prepubertal and pubertal children of both sexes (P < 0.001). There is a close linear correlation between the sum of serum IGF-I plus IGF-II levels vs. serum IGFBP-3 (r = 0.724; P < 0.0001). In contrast, there is a nonlinear correlation between serum IGF-I vs. serum IGFBP-3 (concave curve) as well as between serum IGF-II and serum IGFBP-3 (convex curve). A negative correlation was found between serum IGF-I vs. IGFBP-1 (r = -0.51; P < 0.0001) as well as between the sum of serum IGF-I plus IGF-II vs. IGFBP-1 (r = -0.47; P < 0.0001), but not between serum IGF-II and IGFBP-1. These data emphasize that when these tests are performed in the clinic, their interpretation should be based upon age- and sex-specific criteria.

Growth in malnutrition related to gastrointestinal diseases: coeliac disease.

Coeliac disease in children is frequently associated with a slow growth rate. This observation may be linked to the malabsorption that occurs in these patients; however, the underlying mechanism remains unknown. To better understand this phenomenon, we have studied the growth patterns of 153 patients with coeliac disease for 2-9 years. Gastro-intestinal biopsies were performed before and after gluten exclusion. In a second group of 79 children, somatostatin levels and binding properties in the plasma and jejunal mucosa were measured. In a third group of 40 patients we measured insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGF-BP3) levels. We found that in children diagnosed before 2 years of age weight was the most affected growth parameter. In children diagnosed after this age, height was more affected. Suppression of gluten intake induced an acceleration of growth velocity. Although plasma levels of somatostatin were not significantly altered, somatostatin concentrations in the jejunal mucosa of patients in the active phase of the disease were significantly elevated (p < 0.05). Children with coeliac disease exhibited significantly lower levels of IGF-BP3 when compared to patients with normal stature and growth velocities. In contrast, these patients showed an increase in IGF-BP3 levels after gluten exclusion from the diet.

Effect of calcitriol on insulin secretion in uraemia.

To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.

Effects of L-thyroxine treatment on pituitary GH content of adult rats with neonatal thyrotoxicosis.

Rats receiving large doses of thyroxine (30 micrograms/5 doses) during their first days of life develop an apparently permanent alteration of the hypothalamus-pituitary-thyroid complex. This neonatal thyrotoxicosis has been called neo-T4 syndrome. A state of permanent but not very severe hypothyroidism seems to be induced, accompanied by a decrease in pituitary GH content at least until day 22. In this work, growth hormone content has been measured by a specific radioimmunoassay in the anterior pituitary of 45 and 78 day old neo-T4 and control (saline-injected) rats. GH content of the adult neo-T4 treated animals was significantly lower than that of the adult controls. Administration of different doses of T4 (1.7 micrograms/100 g body weight/3 doses or 2.5 micrograms/100 g body weight/8 doses, to 70 day old rats, and 5 micrograms/100 g body weight/3 doses to 42 day old rats) to adult neo-T4 rats did not alter these decreased pituitary GH levels. This differs from hypothyroid rats, in which T4 administration has been shown to increase pituitary GH content. A third approach was to thyroidectomize neo-T4 and control rats and administer 5 micrograms T4/100 g body weight, which produced the same increase in pituitary GH in both groups of animals. These results seem to indicate that changes in pituitary GH content of neo-T4 rats are not due to hypothyroidism. Thus, it would appear that treatment with large T4 doses during the early perinatal period not only deranges the hypothalamic-pituitary-thyroid axis but other pituitary functions as well.

[Kidney and osseous responsiveness to PTH in a case of pseudohypoparathyroidism (author's transl)]. / Resistencia renal y ósea a la PTH en un caso de pseudohipoparatiroidismo.

A case of pseudohypoparathyroidism is described, finding in addition to the typical clinical data described in the literature an all almost total atrophy of the minor lips and clitoris, a perforated hymen and a "paradoxical" increase of convulsions with anticomicial treatment. Study of response of urinary phosphates and AMPc to PTH, was negative (Drezner type I). Osseous response to PTH was negative (Frame type I pseudohypoparathyroidism). Pathogenic possibilities are discussed.

Thyrotrophin and prolactin response to beta-(pyrazolyl-1)-alanine-2-TRH in normal males.

Synthetic beta-(pyrazolyl-1)-alanine-2-TRH, an analog of thyrotropin releasing hormone (TRH) was administered intravenously in doses of 50, 100 and 200 micrograms to four normal men in order to establish the range of responses of TSH and prolactin. Every subject showed a clear elevation in TSH and prolactin levels with all three doses. These results were compared with the increments in TSH and prolactin after the administration of the same doses of synthetic TRH. The computations of potency for absolute levels and/or increments in TSH and prolactin at 20 and 40 min showed that the analog was at least twice as active as TRH in releasing TSH and prolactin.

Changes in parameters of growth hormone and thyrotrophic hormone, and of thyroid function, during the early postnatal period in the rat.

The body length, and the weight of the body, liver, kidney and brain have been measured daily in rats during the first 10 days after birth. The plasma and pituitary growth hormone and thyrotrophic hormone levels were also determined, as well as the thyroidal 127I content and the plasma PBI. This observation period comprises a critical stage during which administration of large doses of thyroid hormones result in a permanent derangement of the thyroid-pituitary interrelations, and impairment of body growth and pituitary GH economy. The rate of growth of body, liver and kidney has been found to decrease significantly from day 7th to 9th of post-natal age, later to increase again. The pattern of the changes observed in the plasma and pituitary GH levels during the same period might well account for the alterations in growth patterns. The rate of growth of the brain, however, is not decreased during this stage, and appears to be independent of the changes in GH economy. No clearcut pattern of changes was observed in plasma TSH level; the pituitary TSH and thyroidal 125I contents increased progressively during the entire observation period. Plasma from suckling rats often contained high concentrations of non identified iodinated compounds, which were not thyroid hormones. Results are discussed in terms of the possible relationships between thyroid hormone and GH economy during a critical developmental period.

Effects of thyroidectomy and thyroxine on plasma growth hormone and insulin levels in rats.

Plasma growth hormone and insulin levels were measured in normal, thyroidectomized (TX), and TX rats treated with 1-thyroxine (1-T4) or rat-growth hormone (r-GH). Although normal growth was observed 5 days after surgery, a decrease of circulating levels of GH was evidenced as early as 5 days after the operation. However, the plasma insulin levels were not affected by the 5th, 10th and 15th day of thyroidectomy. With a more prolonged thyroid hormone deprivation, the plasma insulin levels of TX rats remained lower than those of age-paired controls. Treatment of hypothyroid rats with 0.05 micron 1-T4 for 10 days induced growth and an increase in circulating GH levels, but had no effect on the low levels of plasma insulin of TX rats. Treatment of TX animals with 0.10 or 0.20 micron 1-T4, or 100 micron r-GH during 10 days caused plasma insulin levels to shift toward the values of their weight-paired controls. However, treatment of hypophysectomized (HX) rats with 0.20 micron T4 during 8 days did not change the circulating levels of plasma insulin. It is suggested that thyroid hormone deprivation results in a decrease of circulating levels of insulin secondary to a deficiency in growth hormone secretion. In addition, normal GH secretion appears to be required for normal pancreatic insulin secretion to occur.

Effects of small doses of L-thyroxine and triiodo-L-thyronine on pituitary LH content of thyroidectomized rats.

Pituitary LH was studied by means of a specific radioimmunoassay (RIA) in male rats at different time intervals after thyroidectomy (T), and in rats which were T at least 30 days before and were then treated with different doses of L-thyroxine or triiodo-L-thyronine. A decrease in the pituitary LH of the T animals, with respect to the intact age-paired controls, was demonstrable from 13 days after the operation, when total pituitary LH content was taken into consideration, or from 5 days after T, when the LH concentration (mug/mg pituitary) was considered. Doses of thyroid hormones lower than the daily maintenance dose for the rat produced very little effect on the pituitary LH levels of T animals. However, a single dose of 1.75 mug of T4 or 0.2 mug of T3 (doses approximately equivalent to the T4 and T3 maintenance dose for T rats) induced such a rapid and intense increase in the pituitary LH content that it no longer differed from that of the intact age-paired controls by 12 hours. Surprisingly, 5.0 mug of T4 and 1.0 mug of T3 did not produce any increase in the pituitary LH content of T rats.

Decreased pituitary growth hormone content in rats treated neonatally with high doses of L-thyroxine.

Growth hormone and thyrotrophic hormone content have been measured by specific radioimmunoassays in anterior pituitaries of 22 day old rats. These animals were injected with saline or very high doses of L-thyroxine during the neonatal period in order to induce the "neo-T4" syndrome. Growth of such animals is known to be affected. It was found that not only TSH but also GH content of the T4-treated animals was significantly lower than that of the saline-injected controls.

[Dynamics of growth hormone secretion in patients with primary hypothyroidism, before and after treatment with thyroideal hormones]. / Dinámica de secreción de hormona de crecimiento en pacientes con hipotiroidismo primario, antes y después del tratamiento con hormonas tiroideas

Growth hormone (GH) secretion was studied in a group of alut controls and a series of patients with primary hypothyroidism before and after treatment with thyroid hormones. Intravenous insulin-induced hypoglycemia was the stimulus used (0,1 UI/kg body weight). It is concluded that in primary hypothyroidism, GH secretion is almost absent due to relative inactivity of the somatotropic cells and/or lack of GH-RH. This decreased secretory response becomes rapidly normal after treatment with physiological doses of thyroid hormones.

[Secretion of growth hormone in hyperthyroidism]. / Secreción de hormona de crecimiento en el hipertiroidismo

The authors studied growth hormone (GH) secretion in a group of adult controls and another group of hyperthyroid patients after stimulation with intravenous insulin-induced (0,1 IU/kg) hypoglycemia, aiming to clear out the problem of discrepancies in literature concerning GH secretion in hyperthyroidism. They concluded that in this syndrome, GH levels are significantly higher than those of controls. The GH releasing response is normal, though it could be expected to be decreased due to decreased pituitary GH contents as a result of permanent somatotrophic cell stimulation.