Consequences of targeted treatments for second-line therapy.

The paradigm for first-line treatment of relapsed or metastatic non-small cell lung cancer (NSCLC) is changing. Large phase III trials demonstrated that, in 2010, we cannot select a therapy without an accurate definition of tumor histology and epidermal growth factor receptor (EGFR) status. Patients harboring an EGFR-activating mutation have a better prognosis and certainly are extremely sensitive to EGFR-tyrosine kinase inhibitors, while other agents, such as bevacizumab or pemetrexed, are more effective and less toxic in patients with non-squamous histology. Moreover, data from large phase III trials demonstrated that maintenance therapy with pemetrexed, docetaxel or erlotinib is an effective strategy against metastatic NSCLC. Overall, the changing paradigm in first-line treatment of NSCLC inevitably is changing the second-line strategy. In addition, the emerging role of maintenance therapy is leading to early use of all agents potentially active in a second- or third-line setting, with the consequence that very few options are available at disease progression. The aim of this article is to discuss the consequences of targeted treatments for second-line therapy in metastatic NSCLC.

The role of sex hormone replacement therapy on self-perceived competence in adolescents with delayed puberty.

The objective of the present study was to determine the role of sex steroids in the development of self-perceived competence during adolescence. The Harter Self-Perception Scale was administered to 56 adolescents with delayed puberty who were receiving depo-testosterone (males) or conjugated estrogens (females) administered in 3-month blocks alternating with placebo. Treatment was given at three dose levels approximating early, middle, and late pubertal replacement levels. Hormone treatments had a significant positive effect for both males and females in one subscale domain--perceived job competence. Significant positive hormone effects were also obtained for perceptions of romantic appeal and close friendship in females and perception of athletic abilities in males. It can be inferred from the results of this study that the hormonal changes associated with sexual maturation have targeted influences on specific domains of self-perceived competence and that there are clear gender differences.

Children with organic growth hormone deficiency have elevated cortisol responses to stimuli.

The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPA) function in children with GH deficiency. Ninety-four patients were evaluated for GH deficiency and cortisol (F) deficiency using clinical criteria and L-dopa and insulin-induced hypoglycemia stimulation tests. They were assigned to three diagnostic groups: organic GH deficient (OGHD), idiopathic GH deficient (IGHD), and not GH-deficient (NGHD). Time series, cross-sectional, regression analysis revealed statistically significantly elevated F [>828 nmol/L (30 microg/dL)] in the OGHD group vs. the NGHD group. The value for F in the IGHD group was not different from the NGHD group. This finding suggests that dysregulation of the HPA axis is present in most children with OGH deficiency and significantly less often in children with IGH deficiency or without GH deficiency. Anatomical disruption of the control pathways for the HPA axis or stress may cause the dysregulation.

Self-assessment of physical sexual maturation in boys and girls with delayed puberty.

We studied 49 boys and girls with delayed physical sexual maturation during treatment with sex steroids. We found significant agreements, but also some disagreements between physicians' and subjects' Tanner sexual maturity ratings. We found neither effects of treatment with sex steroids nor gender differences, comparing ratings between physicians and patients.

The effect of sex hormone replacement therapy on behavior problems and moods in adolescents with delayed puberty.

OBJECTIVE: The objective of this clinical study was to determine the effects of sex steroids on behavior and mood in adolescents with hypogonadism. STUDY DESIGN: The experimental design consisted of a randomized, double-blind, placebo-controlled, crossover trial lasting for 21 months. The study group consisted of 39 boys and 16 girls recruited from a pediatric endocrine clinic for delayed puberty. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks, alternating with placebo, at 3 dose levels approximating early, middle, and late pubertal amounts. The Child Behavior Checklist, Youth Self Report, Differential Emotion Scale, and Daily Mood Diary were administered after each placebo and treatment period to ascertain the effect of sex steroids on self- and parent-reported behavior problems and moods. RESULTS: The data demonstrated only one significant treatment effect, namely, an increase in withdrawn behavior problems during administration of low-dose estrogen in girls. There were no consistent sex differences. CONCLUSION: These results demonstrate that administered testosterone or estrogen has minimal effects on behavior problems or mood in adolescents.

Effects of estrogen or testosterone on self-reported sexual responses and behaviors in hypogonadal adolescents.

The purpose of this study was to investigate the effects of administration of sex steroids on self-reported sexual responses and behaviors in hypogonadal adolescents. We used a randomized, double blind, placebo-controlled, cross-over, clinical trial as the experimental design. The subjects were 39 boys and 16 girls with delayed puberty. We treated girls with oral conjugated estrogen and boys with testosterone enanthate in 3 dose levels intended to simulate early, middle, and late pubertal levels. We administered a modification of the Udry sexual behavior questionnaire after each 3-month placebo and treatment period to detect the effect of sex steroids on self-reported sexual behaviors and responses. We employed a strict intent to treat statistical analytical model. The data showed significant effects of the administration of testosterone to boys causing increases in nocturnal emission and touching behaviors at the mid- and high doses. No other treatment effects on sexual behaviors or responses were seen in boys. For girls, there was a significant increase in necking caused by the administration of estrogen only at the late pubertal dose. No other treatment effects on sexual behaviors or responses were seen in girls. We noted some gender differences for thinking about sex, sexual "turn-on," and the nature of sexual behavior. The administration of physiological doses of sex steroids to boys or girls with delayed puberty have few effects on sexual behaviors and responses.

Estrogen or testosterone increases self-reported aggressive behaviors in hypogonadal adolescents.

A randomized, double-blinded, placebo-controlled cross-over clinical trial was used to determine the role of sex steroids on the development of aggressive behaviors in 35 boys and 14 girls. Depo-testosterone (to boys) or conjugated estrogens (to girls) was administered in 3-month blocks alternating with placebo at three dose levels approximating early, middle and late pubertal amounts. The Olweus Multifaceted Aggression Inventory was administered after each placebo and treatment period to ascertain the effect of sex steroids on self-reported aggressive behaviors. We employed a strict intent-to-treat analytical model. The data demonstrated significant hormone effects on physical aggressive behaviors and aggressive impulses, but not in verbal aggressive behaviors nor aggressive inhibitions in both boys and girls. These results are the first to causally relate the administration of physiological doses of sex steroids to changes in aggressive behaviors in adolescents.

Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

Correction of syndactyly using a dorsal omega flap and two lateral and volar flaps. A long-term review.

The long-term results of a technique for correction of syndactyly are reported. The technique consists of a dorsal omega flap and a palmar anchor forming two palmar and lateral flaps. A long-term review was made of 50 patients with a minimum of 8 years follow-up operated over a period of 10 years. A total of 122 web spaces in simple, complex and syndromic syndactyly were operated on. Most patients achieved satisfactory reconstruction of the web spaces, resulting in a web of good shape. At long-term review, web creep was recorded in eight webs, and skin contractures in three fingers. This study shows the technique to be effective in reconstructing web spaces and in minimizing the prevalence of complications.

Tissue expanders in syndactyly: a brief review.

Tissue expansion has been advocated as a method of obtaining enough skin to correct syndactyly without using skin grafts. However, results have been disappointing, indications are unclear, and complication rates are still relatively high. We review the published cases of syndactyly treated with tissue expansion, acknowledging the lack of data and guidelines for its use in such condition. After more than 10 years since its introduction in the treatment of syndactyly, its use is still not as widespread as one would have been led to expect.

Injuries to the nail bed in childhood.

Many fingertip injuries in childhood involve the nail bed. Deformities of the nail are a frequent result of failure to repair the nail bed at the time of injury. Secondary correction of nail deformities seldom achieves good results. We present the results of our experience in the management of 19 children with 22 injuries involving the nail bed. All achieved normal nail growth and the overall result of the repair was good in 91%. Complications were few and parental satisfaction with the management was high. Every effort should be made to perform a meticulous primary repair of all nail bed injuries.

Traumatic release of Dupuytren's contracture.

A case of partial traumatic division of a Dupuytren's band in a 56-year-old man with known Dupuytren's disease is described. Management consisted of exploration of the wound and limited fasciectomy, with excision of the diseased fascia, the pretendinous band, the lateral cord and the spiral cord. Postoperative recovery was uneventful, and the patient returned to work. He remains well two years after the injury.

[Magnetic resonance in thoracic pathology: characterization by intensity values]. / Risonanza magnetica in patologia toracica: tipizzazione con rilievi di intensità.

The authors examined prospectively 100 patients with lung diseases--50 of them benign and 50 malignant. The mean value of all lesions was measured with a constant region of interest (ROI); the muscle was considered as the reference tissue. Histopathology was the gold standard for the patients who underwent CT-guided needle biopsy and/or surgery; clinical-radiologic follow-up (average time: 2 years) was the gold standard for nonsurgical patients. A superconductive 1.5-T magnet with circular polarization body coil was used; T1- and T2-weighted spin echo images were acquired on the coronal and axial planes, respectively. The mean values with the constant ROI were measured both on the lesions and on the reference tissue to calculate and compare the T1-lesion/T1-muscle and T2-lesion/T2-muscle ratios in benign and malignant conditions. The t-test, the linear regression and correlation test and the analysis of variance were used to analyze the data. T1 benign lung disease/T1 muscle ratio was 1.21, while T1 malignant lung disease/T1 muscle ratio was 1.27, with no statistically significant difference. T2 benign lung disease/T2 muscle ratio was 2.63, while T2 malignant lung disease/T2 muscle ratio was 4.80: the difference was statistically significant (p < 0.001). To conclude, in chest diseases, the measurement of mean values in T2 allowed malignancy-indicative values (> 4 ratio) and positively benign values (< 2.5 ratio) to be identified.

[Integrated cardiorespiratory changes induced by chemical stimulation of muscular receptors]. / Modificazioni integrate cardiorespiratorie indotte da stimolazione chimica di recettori muscolari.

Muscular exercise is accompanied by evident and perfectly matched cardiovascular and respiratory adjustments to avoid changes in arterial blood gases. The mechanisms responsible for this perfect regulation have not yet been defined. Our previous experimental investigations have shown that a consistent rate of cardiorespiratory reflex responses to exercise is caused by chemosensitive muscular receptors activation. The 2 different types of classical muscular exercise (rhythmic and isometric exercise) are joined with the 2 different patterns of cardiorespiratory reflex responses attributed in our opinion to the activation of 2 different kinds of muscle receptors (K and P). It has been observed that the increase in ventilation (VE), elicited by activation of both types of chemoreceptors during muscular experimental exercise is not accompanied by significant variations of partial pressure of CO2 (PaCO2) in the arterial blood (isocapnic hyperpnea). This suggest that muscular chemoreceptor activation during physical exercise determines an adequate cardiopulmonary matching. The main purpose of the present study has been to verify, in anesthetized rabbits, if also the chemical activation of muscular receptors was able to evoke reflexly an adequate degree of cardiopulmonary matching. The ventilation reflex changes and the concomitant variations of PaCO2 induced by injection of bradikinin (BK 250 ng) and hypertonic solutions (NaCl 10% 1 ml) in femoral artery have been evaluated in 10 anesthetized rabbits. The PaCO2 modifications observed during reflex hyperpnea have been compared with those recorded during hyperpnea induced by artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)