Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

[Effect of an 8-week aerobic training program during physical education lessons on aerobic fitness in adolescents]. / Efecto de un programa de entrenamiento aeróbico de 8 semanas durante las clases de educación física en adolescentes.

OBJECTIVE: To determine the effect of a high intensity aerobic training program of 8 weeks, developed during physical education classes, on the aerobic capacity of adolescents aged 15 to 18 years. METHODS: A total of 84 adolescents (51 boys and 33 girls) participated in this study. The aerobic capacity (VO(2)max) was measured directly with a portable gas analyzer (K4b², Cosmed) during the performance of the 20 Meters Shuttle Run Test (20mSRT). The sample was divided into 2 experimental groups (G2S and G3S) and 1 control group. The training program was composed of aerobic physical activity (75-80% VO(2)max.). The G2S developed 2 sessions per week while the G3S made 3. RESULTS: The G2S increased VO(2)max (boys: from 55.7 to 56.6 ml/kg/min; girls: from 37.8 to 38.7 ml/kg/min; p < 0.001) and the number of stages in the 20mSRT (9.0% boys, p < 0.001; 20.0% girls, p < 0.001). The G3S also increased VO(2)max (boys: from 54.9 to 56.0 ml/kg/min; girls: from 36.0 to 38.7 ml/kg/min) and the number stages in the 20mSRT (10.4% boys, p < 0.001; 32.3% girls, p < 0.001). In G2S and G3s, girls showed greater improvement than boys. CONCLUSIONS: A high intensity aerobic training program developed during 8 weeks, 2 sessions per week, improves aerobic capacity of the students. An extra session of intense exercise for week is a greater improvement in girls, but do not produce such effects in boys.

Efecto de un programa de entrenamiento aeróbico de 8 semanas durante las clases de educación física en adolescentes / Effect of an 8-week aerobic training program during physical education lessons on aerobic fitness in adolescents

Objetivo: Determinar el efecto de un programa de entrenamiento aeróbico de alta intensidad de 8 semanas, desarrollado durante las clases de Educación Física, sobre la capacidad aeróbica de adolescentes de 15 a 18 años. Método: Un total de 84 adolescentes (51 chicos y 33 chicas) participaron en el presente estudio. La capacidad aeróbica (VO2max) se midió directamente con un analizador de gases portátil (K4b2, Cosmed) durante la realización del 20 Meter Shuttle Run Test (20mSRT). La muestra fue dividida en 2 grupos experimentales (G2S y G3S) y 1 grupo control. El programa de entrenamiento consistió en la práctica de actividad física aeróbica con una intensidad equivalente al 75-80% del VO2max. El G2S realizó 2 sesiones semanales mientras que el G3S realizó 3 sesiones. Resultados: El G2S incrementó el VO2max (de 55,7 a 56,6 ml/kg/min los chicos; de 37,8 a 38,7 ml/kg/min las chicas, p < 0,001) y el n.o stages en el 20mSRT (9,0% los chicos, p < 0,001; 20,0% las chicas, p < 0,001). El G3S también aumentó el VO2max (de 54,9 a 56,0 ml/kg/min los chicos; de 36,0 a 38,7 ml/kg/min las chicas) y el n.o stages en el 20mSRT (10,4% los chicos, p < 0,001; 32,3% las chicas, p <0,001). En G2S y G3S, las chicas mostraron una mayor mejora que los chicos. Conclusiones: Un programa de entrenamiento aeróbico de alta intensidad de 8 semanas, 2 días por semanas, mejora la capacidad aeróbica de los alumnos. Una sesión extra de ejercicio intenso por semana supone una mayor mejora en las chicas, no produciendo tales efectos en los chicos (AU)

Objective: To determine the effect of a high intensity aerobic training program of 8 weeks, developed during physical education classes, on the aerobic capacity of adolescents aged 15 to 18 years. Methods: A total of 84 adolescents (51 boys and 33 girls) participated in this study. The aerobic capacity (VO2max) was measured directly with a portable gas analyzer (K4b2, Cosmed) during the performance of the 20 Meters Shuttle Run Test (20mSRT). The sample was divided into 2 experimental groups (G2S and G3S) and 1 control group. The training program was composed of aerobic physical activity (75-80% VO2max.). The G2S developed 2 sessions per week while the G3S made 3. Results: The G2S increased VO2max (boys: from 55.7 to 56.6 ml/kg/min; girls: from 37.8 to 38.7 ml/kg/min; p < 0.001) and the number of stages in the 20mSRT (9.0% boys, p < 0.001; 20.0% girls, p < 0.001). The G3S also increased VO2max (boys: from 54.9 to 56.0 ml/kg/min; girls: from 36.0 to 38.7 ml/kg/min) and the number stages in the 20mSRT (10.4% boys, p < 0.001; 32.3% girls, p < 0.001). In G2S and G3s, girls showed greater improvement than boys. Conclusions: A high intensity aerobic training program developed during 8 weeks, 2 sessions per week, improves aerobic capacity of the students. An extra session of intense exercise for week is a greater improvement in girls, but do not produce such effects in boys (AU)

[Pelvic lymphadenectomy as an alternative to adjuvant radiotherapy in early stage endometrial cancer at high risk of recurrent lymphatic metastases (stage I)]. / Linfoadenectomia pelvica come alternativa alla radioterapia adiuvante nel carcinoma endometriale ad alto rischio di metastasi linfonodali in fase precoce (stadio I).

AIM: The aim of this study was to evaluate if the surgical approach without pelvic lymphadenectomy and with adjuvant radiotherapy in the patients suffering from endometrioid adenocarcinoma type at high risk (of lymphatic metastasis) in early stage can be substituted by only surgery with pelvic lymphadenectomy (with or without para-aortic lymphadenectomy). METHODS: A retrospective study was carried out on 56 patients who underwent surgery with eventual adjuvant radiotherapy and were attended during the follow-up in the Operative Unit of Gynecology and Obstetrics from 1997 to 2004. The patients were divided into two groups: the low risk group and the high risk group. The cancer grading (G) was defined before the surgery with an hystological exam on endometrial biopsies. The follow-up had a medium duration of 30 months (range: 9-44 months) and consisted of the evaluation of: cancer related survival (CRS); recurrence free survival (RFS). Both were evaluated according to age, risk type, and therapy adopted. RESULTS: Four patients (7.1%) showed relapse during the period of study in a medium time of 24 months (range: 12-36): 2 of these patients (C and D cases; 36%) had a relapse both locally (pelvic wall) and distantly; the other two (A and B cases; 36%) had only a distant relapse. None of the patients at the stage IA had a relapse, but it occurred in the 8.7% of the cases (N.=2) IB and in the 10.5 % of the patients IC (N.=2). One patient of the low risk group (3.8%) (case A) had a distant relapse (lungs) 12 months after the surgery and died 6 months after the appearance of the relapse without any additional treatment, because of age and of concomitant pathologies which suggested another illness. Three patients of the high risk group (10%) had a local and /or distant relapse (one only distant, two both distant and local). One of them with distant relapse (36 months after the primary treatment) (case B) is still alive, even though she has got a controlled cancer, 8 months after the rescue treatment (chemotherapy), whereas two of them died in a medium time of 14 months (range 13-15 months) from the rescue treatment (C and D cases). One of the three patients of the high risk group underwent the standard surgical treatment with lympho-adenectomy (case B) whereas the other two underwent the standard surgical treatment with aiding radiotherapy (C and D cases). The CRS and the RFS were 96.2% and 96.2% in the low risk group, 93.3% and 90% in the high risk group, respectively. CONCLUSIONS: The standard surgery offers a good prognosis to the low risk group patients. To the high risk group the CRS and the RFS were better with standard surgery with lymphadenectomy than with standard surgery with adjuvant radiotherapy. The degree of differentiation of the cancer is the most important prognostic factor in relation to the survival free from relapse (RFS).

Chance-corrected measures of reliability and validity in K x K tables.

When studying the degree of overall agreement between the nominal responses of two raters, it is customary to use the coefficient kappa. A more detailed analysis requires the evaluation of the degree of agreement category by category, and this is carried out in two different ways: using the value of kappa in the collapsed table for each category or using the agreement index for each category (proportion of agreements observed). Both indices have disadvantages: the former is sensitive to marginal totals; the latter is not chance corrected; and neither distinguishes the case where one of the two raters is a gold standard (an expert) from the case where neither rater is a gold standard. This article suggests five chance-corrected indices which are not sensitive to marginal totals and which differ depending on whether there is a standard rater. The article also justifies the reason for poor performance of kappa when the two marginal totals are unbalanced (especially if they are so in opposite directions) and the reason for its good performance when analysing the various 2 x 2 tables obtained by the collapse of a wider table.

Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause.

The menopausal status is associated with an increased risk of metabolic and cardiovascular diseases. Since the post-menopausal modifications have not been clearly investigated in obese women, we evaluated the influences of menopausal status on anthropometric, hormonal and biochemical characteristics in selected groups of normal-weight and obese women. We studied 92 female outpatients: 24 normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age 44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44, age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6 +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2 +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes or impaired glucose tolerance (IGT). Anthropometric parameters, body composition, 17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were determined. Free androgen index (FAI) and insulin resistance index (HOMA) were calculated. In comparison with Pre-OB, Post-OB had higher values of waist circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL-cholesterol were high in Post-NW women, whereas in the obese subjects they were already elevated in the premenopausal period. SHBG levels declined and FAI increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively correlated with waist values. Serum leptin levels were higher in Post-OB than in Pre-OB, whereas they were similar in normal-weight women. The rise of leptin levels may be related to the greater abdominal fat deposition. In addition, menopausal status of uncomplicated obese women is associated with a greater abdominal fat deposition and with higher values of free androgen index, which may be considered as factors of cardiovascular risk.

Delta: a new measure of agreement between two raters.

The most common measure of agreement for categorical data is the coefficient kappa. However, kappa performs poorly when the marginal distributions are very asymmetric, it is not easy to interpret, and its definition is based on hypothesis of independence of the responses (which is more restrictive than the hypothesis that kappa has a value of zero). This paper defines a new measure of agreement, delta, 'the proportion of agreements that are not due to chance', which comes from model of multiple-choice tests and does not have the previous limitations. The paper shows that kappa and delta generally take very similar values, except when the marginal distributions are strongly unbalanced. The case of the 2 x 2 tables (which admits very simple solutions) is considered in detail.

Absorption and distribution of naproxen in rats orally treated with naproxen betainate sodium salt monohydrate. Comparison with naproxen.

The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin) was synthesized to improve bioavailability and tolerability of naproxen. 24 albino rats were treated with naproxen-betaNa (84 mg/kg) and 24 with S-naproxen (naproxen) (50 mg/kg) by the oral route, the doses being equimolar. The animals were sacrificed and naproxen was assayed in timed plasma samples drawn off over a 24-h period and in tissues excised 1 h after administration. Peak concentrations of naproxen proved to be higher with naproxen-betaNa than with naproxen as such. The area under the curve of naproxen concentrations observed with the two administrations overlapped as did concentrations of the drug in the lungs, myocardium and liver. Naproxen concentrations in the gastric wall after naproxen-betaNa proved to be lower than after administration of naproxen as such, which allowed the authors to assume that naproxen-betaNa has a better gastric tolerability.

Comparative bioavailability study on naproxen betainate sodium salt monohydrate and naproxen sodium salt in healthy volunteers.

The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin, test drug), and the sodium salt of S-naproxen (reference), were administered to twelve healthy volunteers of both sexes according to a crossover design, in a single dose of one 575 mg capsule of test, containing 342 mg of S-naproxen and two 275 mg tablets of reference, containing 502 mg of S-naproxen. Blood samples were drawn off over a 24-h period before (time 0) and after administration at foreseen time intervals. Naproxen was measured in plasma by a validated HPLC assay with UV detection which was able to detect 1 microgram/ml and proved to be linear in the range 1-100 micrograms/ml. The non-compartmental pharmacokinetic parameters obtained were statistically processed according to the EU guidance note on bioavailability and bioequivalence Cmax, AUC0-24h and AUC0-infinity were normalized to the dose of 502 mg of naproxen and log-transformed before statistical analysis to assess bioequivalence. Dose-normalized values of plasma concentrations encountered with the two formulations proved to overlap, with the exception of the first sampling time which showed naproxen concentrations that were higher with test drug than with reference. The specific test for bioequivalence led to 90% confidence intervals within the 80-125% range with target pharmacokinetic parameters, whereas the time to peak (tmax) observed with the test and reference drugs did not differ to any statistically significant degree when analysed with Wilcoxon's non-parametric test. It is concluded that the test drug should be declared bioequivalent with the reference drug in terms of dose-normalized concentrations, despite the more rapid increase in plasma concentrations of naproxen observed at the first sampling time with test drug.

Myocardial fatty acid pattern in rats fed on an erucic acid enriched diet.

Individual lipid classes and their fatty acid pattern in myocardium of rats fed on a diet containing 10% erucic acid ethyl ester (cis-13-docosenoic acid ethyl ester) were investigated and compared to rats fed on a normal diet. Two groups of rats were treated for 10 consecutive days with the erucic acid ethyl ester diet and the standard diet, respectively. After extracting total lipids from the myocardium of the rats, the individual lipid classes and the percentage of fatty acids in phospholipids, free fatty acids, diglycerides and triglycerides were measured. The data obtained demonstrate that the erucic acid ethyl ester diet induces a marked increase in free fatty acids and in triglycerides and marked differences in fatty acid pattern in triglycerides, free fatty acids and diglycerides, but only marginal differences in phospholipids, which seem to be carefully preserved as fundamental components of cell and mitochondria membranes.

[Kerion of the vulva. Report of a case and review of the literature]. / Kerion a localizzazione vulvare. Descrizione di un caso e revisione della letteratura.

We report a case of a 43 year old woman who developed an extensive vulvar kerion caused by Trichophyton menthagrophytes that was initially mistaken for a bacterial infection. The peculiarity of this case lies in the fact that the kerion is rarely located in the vulva and it has not yet been described in the literature. On the contrary, cases have been found in the scalp, beard, eye-brow, etc. We discuss the etiopathogenetic aspects, criteria for differential diagnosis and therapy management of this rare clinical picture.