Homocisteina plasmática como factor pronóstico de mortalidad en pacientes con fractura de cadera / Plasmatic homocysteine as prognostic factor for mortality for patients with hip fracture

Introducción y objetivos: Los objetivos del estudio fueron describir la población sometida a cirugía por fractura de cadera, valorar la incidencia de morbilidad y mortalidad e identificar los factores pronósticos asociados a la mortalidad. Pacientes y métodos: Estudio prospectivo, con seguimiento de seis meses después del alta hospitalaria, de pacientes mayores de 64 años sometidos a cirugía de fractura de cadera en el Hospital Santa Bárbara, Soria (España). Se estudiaron parámetros sociodemográficos, complicaciones clínicas y mortalidad. Resultados: Se incluyó a 97 pacientes, de edad media de 85,86 años (DE 7,61), de los cuales 76,90% eran mujeres. El 83,50% de los pacientes tenían un riesgo anestésico ASA III-IV. La estancia media hospitalaria fue de 14,04 días (DE 4,78). La quinta parte de los pacientes (21,65%) presentaron alguna complicación postoperatoria, principalmente de origen respiratorio. La mortalidad intrahospitalaria fue del 13,20% y de 16,50% a los 6 meses. Los factores pronósticos independientes de mortalidad fueron la infección respiratoria, el riesgo anestésico ASA IV y los niveles elevados de homocisteina. Conclusiones: La fractura de cadera está asociada con una elevada tasa de morbilidad y mortalidad a los seis meses de la intervención. La infección respiratoria, el riesgo anestésico ASA IV y los niveles elevados de homocisteina son factores pronósticos de mortalidad en estos pacientes

Background and objective: The objetive of the study was to describe the population of patients undergoing surgery for hip fracture, to assess the incidence of mortality and identify associated prognostic factors. Patients and methods. A prospective study, with follow-up during six months after hospital discharge, of patients over 64 years old undergoing surgery for hip fracture at Santa Barbara Hospital, Soria (Spain). Variables studied were sociodemographic parameters, clinical complications and mortality. Results. A total of 97patients were included, with a mean age of 85.86 years (7.61), of whom 76.9% were woman and 83.50% were ASA III-IV. The mean hospital stay was 14.04 days (SD 4.78). The figth part (21.65%) of the patients had postoperative complications, the most frequent being respiratory. In hospital mortality was 13.2 % and 16.50% at 6 months. Indepent prognostic factors of mortality after surgery were the respiratory infection, ASA IV anesthesia risk and high levels of homocysteine. Conclusions: Hip fracture is associate with a high post-operative morbidity and mortality rate at six months after surgery. The respiratory infection, ASA IV anesthesia risk and high levels of homocysteine are indepent prognostic factor of mortality in these patients

Total antioxidant capacity and oxidative stress after a 10-week dietary intervention program in obese children.

UNLABELLED: Dietary and serum total antioxidant capacity (TAC) are considered appropriate tools for investigating the potential health effects of dietary antioxidants consumed in mixed diets. The aim was to analyze the impact of a dietary intervention on macronutrient intakes and to evaluate the improvement on oxidative status after weight loss (WL) by measuring dietary and serum TAC, and urinary F2-isoprostane levels as markers of oxidative stress. Forty-four overweight/obese children (mean age 11.5 years) were enrolled to undergo a 10-week WL program. They were dichotomized at the median of body mass index-standard deviation score (BMI-SDS) change, as high (HR) and low responders (LR) after intervention. Subjects were prescribed with a fixed full-day meal diet, calculated according to their basal metabolic rate and physical activity levels. A validated food-frequency questionnaire was used to retrospectively calculate TAC and daily nutrient intake. The HR subjects were able to reduce anthropometric indices and to improve lipid and glucose profile. They also significantly diminished fat intake (p = 0.013). Moreover, baseline serum TAC values did significantly predict the reduction in urinary F2 isoprostane (B = -0.236 (-0.393 to -0.078); p = 0.014) in the HR group after the WL program. Notably, changes in dietary TAC after the treatment were associated with a decrease in body weight after the 10-week intervention (B = -2.815 (-5.313 to -0.318), p = 0.029) in the HR group. The -ΔSerumTAC/ΔDietaryTAC and the -ΔF2Isoprostane/ΔDietaryTAC ratios revealed that the relationships between oxidative markers and antioxidants dietary intake were more favorable in the HR than in the LR group. CONCLUSION: Our study showed that a 10-week WL program was able to reduce adiposity indices in obese children. Moreover, after the intervention changes in dietary TAC and WL were significantly associated. Our result suggests that specific food with a high TAC content (such as fruits, vegetables, and legumes) could be recommended to improve WL.

Management of prolonged epistaxis in pregnancy: case report.

OBJECTIVES: To report a case of life-threatening epistaxis in a pregnant patient, describe the links between pregnancy and epistaxis, and discuss the management of such cases. Life-threatening epistaxis in pregnancy is rare, and there are no specific evidence-based guidelines regarding the management of these patients. CASE REPORT: A 31-year-old primigravida presented with severe epistaxis in the second trimester of her pregnancy. Conservative measures failed, thereby necessitating surgical intervention. CONCLUSION: This case illustrates the importance of a multidisciplinary approach in the management of a pregnant patient presenting with severe epistaxis, and highlights the surgical challenges presented in such a situation.

Efectos de la selección y de la superovulación en las pérdidas gestacionales de ratonas CF1 / Effects of selection and superovulation on gestational losses in CF1 mice

En un par de líneas de ratones seleccionadas para alto (s') y bajo peso (s), originadas a partir de una población no seleccionada de la cepa CF1 (t), se modificó la estructura ovárica. El diámetro de los folículos ováricos y el número de folículos y de cuerpos lúteos se incrementaron en las hembras de la línea s', sin expresarse en un mayor tamaño de camada al nacimiento, posiblemente, por un aumento de las pérdidas gestacionales. Se probó si los efectos conjuntos de la selección de peso a largo plazo y de la estimulación ovárica incrementaban las pérdidas gestacionales. Se utilizaron dos grupos de hembras por línea: sin y con estimulación ovárica (5UI de eCG y 5UI de hCG). Las hembras se sacrificaron a las 56-72 hs y a los 7 días postservicio y después de la primera parición. Se observaron los números de cuerpos lúteos (CL), embriones (E) y sitios de implantación (SI) y el tamaño de camada al nacimiento (TC). Se estimaron las pérdidas totales (PT) y las pérdidas de cuerpos lúteos (PCL), de embriones (PE) y de fetos (PF). Los promedios de CL, E, SI y TC variaron en el mismo sentido de la selección practicada y fueron significativamente mayores (P<0,05) para las hembras estimuladas, a excepción de TC. La línea s' tuvo un potencial reproductivo superior pero un mayor costo biológico (mayor PT y más tardía) cuando se la comparó con las otras líneas. La estimulación ovárica produjo menores eficiencias reproductivas totales para las tres líneas y pérdidas gestacionales mayores y más tardías, principalmente de SI. Las hembras de la línea no seleccionada (t), no estimuladas, con pesos intermedios, parieron un mayor número de crías, partiendo de un número intermedio de CL, E y SI, con una menor y más temprana mortalidad embrionaria, demostrando ser las más eficientes desde el punto de vista reproductivo y productivo.

The ovarian structure was modified as a consequence of weight selection in a pair of mouse lines selected for high (s') and low weight (s). Lines were founded from an unselected population of CF1 strain (t). The follicle diameter and the number of the ovarian follicles and the corpora lutea were higher in s' females, but they did not reach a larger litter size at birth, may be, by an increase in the gestational losses. In these lines, the co-effects of long-term weight selection and ovarian stimulation were tested to evaluate if they increased gestational losses. Two groups of females per line were employed: without and with ovarian stimulation (5UI of eCG and 5UI of hCG). Females were slaughtered at 56-72hs and at 7 days post-breeding and after first parturition. The number of corpora lutea (CL), embryos (E) and implantation sites (SI), and litter size at birth (TC) were observed. Total losses (PT) and corpora lutea (PCL), embryo (PE) and fetus (PF) losses were estimated. Mean CL, E, SI and TC varied in the same direction of the selection made and they were significantly higher (P<0.05) in stimulated females, though not for TC. Line s' had a higher reproductive potential but a greater biological cost (higher and later gestational mortality) when compared with the other lines. Ovarian stimulation produced lower total reproductive efficiencies for the three lines and higher and later gestational losses, mainly for implantation sites. Females from unselected line (t), without ovarian stimulation, with intermediate weights, bore larger litters, starting from an intermediate number of CL, E and SI, with a lower and earlier embryo mortality, showing to be the most efficient from a reproductive and productive point of view.

The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

Monogenic and polygenic models detected in steroid 21-hydroxylase deficiency-related paediatric hyperandrogenism.

AIMS: Hyperandrogenism, although mostly due to polygenic interactions, is monogenic for some enzymatic adrenal deficiencies. This study evaluates mono- and biallelic 21-hydroxylase deficiency (21OHD)-related hyperandrogenism in pediatric patients. Sensitizing and protective polymorphisms were investigated in carriers and cryptic forms of 21OHD. METHODS: The study involved a monogenic analysis of CYP21A2 in patients (375 nonclassical 21OHD [NC21OHD] children; 306 hyperandrogenic 21OHD carriers, n = 306) and a polygenic association study (CAPN10-UCSNP44, PON1-108, TNFR2-M196R, IGF2-ApaI and IRS1-G972R polymorphisms) of 170 hyperandrogenic carriers plus 277 family members (control groups). The metabolic marker 17OH progesterone defined the degree of deficiency; clinical expressivity was determined by pediatric endocrinologists. RESULTS: The group of 21OHD carriers manifesting hyperandrogenism was enriched in the CAPN-UCSNP44 rare variant in homozygosity (4.9 vs. 0.4%, NCBI data for the general population; p = 0.004). In our patients and controls, contrasting distributions were observed for this and another polymorphism, TNFR2-196R. In a recessive model, their rare variants were more frequently detected among the forms with high (p = 0.048) and low (p = 0.034) expressivity respectively. CONCLUSIONS: 21OHD-related pediatric hyperandrogenism follows monogenic and polygenic models. The opposite behaviors in terms of clinical expressivity detected for CAPN-UCSNP44 and TNFR2-M196R rare variants suggest these variants to be sensitizing and protective factors respectively in adrenal hyperandrogenism.

Ovarian structure in mice lines selected for weight.

Selection for body weight at 49 day of age (s and h, downward selected lines; s' and h', upward selected lines) affected reproductive traits in CF1 mice lines. The objective of this study was to compare ovarian structures in females of these lines, as well as in unselected controls (Line t). The number of ovarian follicles (N), follicle diameter (FD), number of corpora lutea (CL), litter size (LS), and body weight (W), were recorded. There were significant differences among lines for N, FD, CL, LS and W; means values for the lines with the greatest difference for post-pubertal females were: N(s) = 19.3 and N(s') = 32.7; FD(h') = 161.7 and FD(s') = 178.2; CL(h) = 10.3 and CL(s') = 21.9; LS(s) = 6.0 and LS(h') = 11.1; W(h) = 18.9 and W(s') = 32.4. There were also differences between positive lines; Line s' had a higher proportion of large follicles in pre-pubertal females, a greater capacity to convert these follicles into CL, but a lower capacity to maintain embryos until term than Line h'. For negative lines, Line h apparently had a reduced incidence of embryonic loss when compared with Line s. In conclusion, selection for body weight modified ovarian structure, as well as reproductive efficiency.

[Low height and rare diseases]. / Talla baja y enfermedades raras.

Low stature is the main reason of consultation in paediatric endocrinology. In a high percentage of cases, its etiology is clear and fundamentally answers to variants of normality. However, in approximately 20% of cases low stature is pathological and requires exhaustive studies. The association of rare diseases (RD) with low height is very frequent. In this article we review the etiology of low height, describing: - The genetic forms of the growth hormone (GH), whether isolated or associated with malformations of the average line or others. - Those which are of great importance due to their clinical repercussion, such as Turner's Syndrome, Noonan's Syndrome and Willi-Prader's Syndrome. - The frequent osseous dysplasias, in some cases with genetic alterations of the SHOX gene, situated in the short arm of the Xp chromosome. The importance of these diagnoses lies in the possibility of carrying out early and efficient treatment, in some of them, with GH. In conclusion, the diagnosis of rare diseases with low height is a current and normal challenge in paediatric endocrinology due to the great advances in molecular genetics and the possibility of treatment in some of them. It always involves a multidisciplinary approach due to the frequent association of pathology it presents, and, in its turn, it offers the possibility of carrying out timely genetic counselling.

Talla baja y enfermedades raras / Low height and rare diseases

La baja talla constituye el primer motivo de consultaen endocrinología pediátrica. En un alto porcentajesu etiología es clara y obedece fundamentalmentea variantes de normalidad. Sin embargo, en aproximadamenteun 20% esta baja talla es patológica y obliga aestudios exhaustivos.La asociación de enfermedades raras (ER) con tallabaja es altamente frecuente. En este trabajo repasamoslas etiologías de la baja talla en enfermedades raras,describiendo:– las formas genéticas de la hormona de crecimiento(GH) bien sean aisladas o asociadas amalformaciones de la línea media u otras.– aquellas de gran importancia por su repercusiónclínica como el Síndrome de Turner, Síndromede Noonan y el Síndrome de Willi-Prader.– Las frecuentes displasias óseas, con alteracióngenética en algunos casos para el gen SHOX,situado en el brazo corto del cromosoma Xp.La importancia de estos diagnósticos radica en laposibilidad de hacer un tratamiento precoz y eficaz, enalgunos de ellos, con GH.En conclusión, el diagnóstico de enfermedadesraras con baja talla es un reto actual y habitual en endocrinologíapediátrica por los grandes avances de lagenética molecular y la posibilidad de tratamiento enalgunas de ellas. Implica siempre un abordaje multidisciplinariopor la asociación frecuente de patología quepresenta y a su vez, ofrece la posibilidad de realizar eloportuno consejo genético

Low stature is the main reason of consultation inpaediatric endocrinology. In a high percentage of cases,its etiology is clear and fundamentally answers tovariants of normality. However, in approximately 20% ofcases low stature is pathological and requiresexhaustive studies.The association of rare diseases (RD) with lowheight is very frequent. In this article we review theetiology of low height, describing:– The genetic forms of the growth hormone(GH), whether isolated or associated withmalformations of the average line or others.– Those which are of great importance due totheir clinical repercussion, such as Turner’sSyndrome, Noonan’s Syndrome and Willi-Prader’s Syndrome.– The frequent osseous dysplasias, in somecases with genetic alterations of the SHOXgene, situated in the short arm of the Xpchromosome.The importance of these diagnoses lies in thepossibility of carrying out early and efficient treatment,in some of them, with GH.In conclusion, the diagnosis of rare diseases withlow height is a current and normal challenge inpaediatric endocrinology due to the great advances inmolecular genetics and the possibility of treatment insome of them. It always involves a multidisciplinaryapproach due to the frequent association of pathologyit presents, and, in its turn, it offers the possibility of carrying out timely genetic counselling

A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population.

OBJECTIVE: The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation. METHODS: The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects. RESULTS: One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations. CONCLUSIONS: The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.

Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis.

BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general population requires that misinterpretations of apparently severe mutations in alleles carrying duplicated genes be avoided. Prenatal treatment prevents virilization in female fetuses and genetic counseling may be offered to couples in which one partner is either a patient or a carrier. This paper proposes a semiquantitative PCR method involving primer extension that distinguishes the severe point mutation Q318X in single gene copy alleles from the normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD carriers or patients, and one fetal sample (as well as the DNA of his family) were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific oligonucleotides hybridization for common mutations, Southern analysis, complementary direct sequencing and microsatellite typing. Primer extension analysis of the Q318X variants using fluorescent dideoxynucleotides was performed on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients, potential carriers and prenatal samples. RESULTS: Different fluorescence patterns were seen for the severe mutation (single gene copy) and the nondeficient (gene-duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M) ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method discriminated between the severe Q318X mutation and the normal Q318X variant in gene duplication, and could be a useful complementary tool in prenatal diagnosis and carrier detection.

Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.

AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex- and age-matched case-control study. Participants were 185 obese and 185 control children (aged 5-18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPAR gamma 2 mutation and BstNI for ADR beta 3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPAR gamma 2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09-4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17-5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPAR gamma 2 and ADR beta 3) was 5.30 (95% CI=1.08-25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43-146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPAR gamma 2 gene and Trp64Arg of the ADR beta 3 gene for obesity risk was found in a case-control study including children and adolescents.

Diabetes mellitus / No disponible

No disponible

Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop) contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21-hydroxylase deficiency) in the Spanish population.

This study addresses the contributions of gene conversion and a founder effect to the distribution of the two most frequent severe point mutations of the 21-hydroxylase (21OH) gene causing congenital adrenal hyperplasia: the 655G splicing mutation at intron 2, and Gln318Stop in a Spanish population. Direct and indirect analyses of segregated mutant and normal 21OH genes in 200 Spanish families (classic and nonclassic 21OH deficiency) were performed. Both mechanisms were found to contribute to different degrees to the defective investigated alleles. The 655G splicing mutation (62 alleles, 15.5%) seemed to be almost exclusively related to recent conversion events, whereas Gln318Stop (33 alleles, 8.3%) is more likely to be due to the dissemination of remotely generated mutant alleles. Other severe defective alleles, 8 bp-deletion (13 alleles, 3.3%), 306insT (5 alleles, 1.3%), and gene deletions (43 alleles, 11%), as well as the mild mutation Val281Leu (120 alleles, 30%), also appear to be strongly associated with particular D6S273 alleles. Although gene conversion contributes to the generation of severe 21OH alleles, the high frequency of some severe mutations in different geographic areas is consistent with a founder effect.

Hipocrecimiento. Consideraciones generales / Hypogrowth. General considerations

El crecimiento es un indicador fundamental del estado de salud del niño. Muchas patologías que ocurren durante la infancia pueden incidir en el mismo y afectar a la talla final de forma evidente. La evolución y seguimiento periódico de la talla y el peso es un control obligado por los pediatras, debiéndose detectar alteraciones tempranas que puedan corresponder a patologías responsables y posibilitar un correcto diagnóstico y tratamiento precoz. El tiempo del crecimiento en la vida de una persona no es largo, y de ello se deriva la importancia de un seguimiento cuidadoso del mismo. En este trabajo se revisarán los factores que interaccionan en el crecimiento, la metodología a seguir en la consulta de atención primaria para establecer un diagnóstico y el seguimiento ante la talla baja. Se incluye la clasificación del hipocrecimiento que permite diferenciar la talla baja denominada idiopática de la patológica (AU)