Inference on an heteroscedastic Gompertz tumor growth model.

We consider a non homogeneous Gompertz diffusion process whose parameters are modified by generally time-dependent exogenous factors included in the infinitesimal moments. The proposed model is able to describe tumor dynamics under the effect of anti-proliferative and/or cell death-induced therapies. We assume that such therapies can modify also the infinitesimal variance of the diffusion process. An estimation procedure, based on a control group and two treated groups, is proposed to infer the model by estimating the constant parameters and the time-dependent terms. Moreover, several concatenated hypothesis tests are considered in order to confirm or reject the need to include time-dependent functions in the infinitesimal moments. Simulations are provided to evaluate the efficiency of the suggested procedures and to validate the testing hypothesis. Finally, an application to real data is considered.

Negative symptoms as key features of depression among cannabis users: a preliminary report.

OBJECTIVE: Cannabis use is frequent among depressed patients and may lead to the so-called "amotivational syndrome", which combines symptoms of affective flattening and loss of emotional reactivity (i.e. the so-called "negative" symptomatology). The aim of this study was to investigate the negative symptomatology in depressed patients with concomitant cannabis use disorders (CUDs) in comparison with depressed patients without CUDs. PATIENTS AND METHODS: Fifty-one patients with a diagnosis of Major Depressive Disorder (MDD) and concomitant CUD and fifty-one MDD patients were enrolled in the study. The 21-Item Hamilton Depression Rating Scale (HDRS) and the negative symptoms subscales of the Positive and Negative Syndrome Scale (PANSS) were used to assess depressive and negative symptomatology. RESULTS: Patients with cannabis use disorders presented significantly more severe negative symptoms in comparison with patients without cannabis use (15.18 ± 2.25 vs 13.75 ± 2.44; t100 = 3.25 p = 0.002). DISCUSSION: A deeper knowledge of the "negative" psychopathological profile of MDD patients who use cannabis may lead to novel etiopathogenetic models of MDD and to more appropriate treatment approaches.

The "Eyeballing" technique: an emerging and alerting trend of alcohol misuse.

OBJECTIVE: Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol "eyeballing", which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, "eyeballing" can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misuse. MATERIALS AND METHODS: Literature on alcohol eyeballing was searched in PsychInfo and Pubmed databases. Results were integrated with a multilingual qualitative assessment of the database provided by The Global Public Health Intelligence Network (GPHIN) and of a range of websites, drug fora and other online resources between March 2013 and July 2013. RESULTS: Alcohol eyeballing is common among adolescents and young adults; substances with high alcohol content, typically vodka, are used for this practice across the EU and internationally. The need for a rapid/intense effect of alcohol, competitiveness, novelty seeking and avoidance of "alcoholic fetor" are the most frequently reported motivations of "eyeballers". Local effects of alcohol eyeballing include pain, burning, blurred vision, conjunctive injection, corneal ulcers or scarring, permanent vision damage and eventually blindness. CONCLUSIONS: Alcohol eyeballing represents a phenomenon with potential permanent adverse consequences, deserving the attention of families and healthcare providers. Health and other professionals should be informed about this alerting trend of misuse. Larger observational studies are warranted to estimate the prevalence, characterize the effects, and identify adequate forms of interventions for this emerging phenomenon.

The role of transforming growth factor-ß1 in airway inflammation of childhood asthma.

TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking.

Novel perspectives in the detection of oral and nasal oxidative stress and inflammation in pediatric united airway diseases.

United airway disease (UAD) concept proposed that asthma and rhinitis are both different clinical manifestation of a single inflammatory process. The aim of this study is to assess in upper and lower airways the level of inflammation and oxidative stress and to investigate the relationship between biomarkers in persistent allergic rhinitis (PER) and in concomitant asthma with PER. By a crosssectional study we measured oral and nasal (FENO) and oral and nasal EBC 8-isoprostane, LTB4 and PGE2 in children with PER (n=14) and with PER and concomitant intermittent asthma (IA; n=25), mild persistent asthma (mA; n=28), moderate persistent asthma (MA; n=13) and in Healthy Controls (HCs; n=13). Oral and nasal FENO concentrations were increased in children with PER, IA, mA and MA when compared with HCs. Nasal 8-isoprostane was higher in EBC of children with PER and asthma than in HCs. Oral and nasal LTB4 were higher in EBC of children with PER and mA than in HCs. Oral and nasal PGE2 concentrations were higher in EBC of children with PER than in HCs. Positive correlations between oral and nasal biomarkers were found in IA for LTB4 and PGE2, in mA for FENO, 8-isoprostane, LTB4 and PGE2, and in MA for PGE2. No correlations were observed in children with PER and HCs. Our results suggest that non-invasive markers of inflammation and oxidative stress might be useful to study the relationships between oral and nasal compartments in allergic children with PER and concomitant asthma with the aim of defining the UAD.

A stochastic model in tumor growth.

A stochastic model of solid tumor growth based on deterministic Gompertz law is presented. Tumor cells evolution is described by a one-dimensional diffusion process limited by two absorbing boundaries representing healing threshold and patient death (carrying capacity), respectively. Via a numerical approach the first exit time problem is analysed for the process inside the region restricted by the boundaries. The proposed model is also implemented to simulate the effects of a time-dependent therapy. Finally, some numerical results are obtained for the specific case of a parathyroid tumor.

Pi* level tuning in a series of diimine ligands based on density functional theory: application to photonic devices.

Energy- and electron-transfer processes are very important for artificial photosynthesis and a variety of other applications. [(bpy)2Ru(PAP)Os(bpy)2]4+ and its oxidized form [(bpy)2Ru(PAP)Os(bpy)2]5+ perform efficient photoinduced energy- and electron-transfer processes, respectively (k(en) = 5.2 x 10(7) s(-1), k(el) = 7.2 x 10(6) s(-1)). The introduction of appropriate donor and acceptor units on the Ru2+ center can improve the lifetime of the excited state, resulting in a much longer and efficient storage of energy. Nonempirical (density functional) calculations and experimental data are used to predict the best donor and acceptor ligands for improving electron- and energy-transfer processes. Such a result can be extended to all polynuclear complexes where electronic coupling between the metal centers is very weak.

Asian sildenafil efficacy and safety study (ASSESS-1): a double-blind, placebo-controlled, flexible-dose study of oral sildenafil in Malaysian, Singaporean, and Filipino men with erectile dysfunction. The Assess-1 Study Group.

OBJECTIVES: To evaluate the efficacy, safety, and tolerability of oral sildenafil in Asian men with erectile dysfunction of various causes (organic, psychogenic, or mixed) and of more than 6 months' duration. METHODS: In this double-blind, parallel-group trial conducted at eight centers in Malaysia, the Philippines, and Singapore, 254 men, 26 to 78 years old, were randomized to 12 weeks of sildenafil or placebo taken as needed 1 hour before anticipated sexual activity. Initially, the sildenafil (n = 127) or matching placebo (n = 127) dose was 50 mg but could be increased to 100 mg or decreased to 25 mg because of a lack of efficacy or intolerance, respectively. Efficacy was assessed by the 15-question International Index of Erectile Function, patients' event logs of sexual activity, and a global efficacy question about erections. RESULTS: The two primary efficacy variables relating to achievement and maintenance of an erection sufficient for sexual intercourse, as assessed by the mean scores for International Index of Erectile Function question 3 (4.22 versus 2.59) and question 4 (4.15 versus 2.41), were both significantly higher with sildenafil than with placebo (P <0.0001). In addition, the five separate International Index of Erectile Function domains of sexual function, the percentage of successful intercourse attempts, and the global efficacy assessment of erections revealed significantly greater treatment effects in favor of sildenafil (P <0.0001 versus placebo for all variables). Treatment-related adverse events occurred in 22.8% of patients who received sildenafil and in 10.2% of those who received placebo. CONCLUSIONS: Sildenafil is an effective and well-tolerated treatment for Asian men with erectile dysfunction of broad-spectrum etiology.

Hydrops foetalis caused by hepatic haemangioma.

The authors report a moderately premature baby with Down's syndrome and hydrops, the latter probably caused by a large hepatic haemangioma which was diagnosed only after birth. At birth the baby was affected by massive right hydrothorax, ascites, hypoalbuminaemia and severe respiratory distress. With the use of modern neonatal intensive care, the baby survived. Corticosteroid treatment (prednisolone 2 mg kg(-1) d(-1) i.v. in divided doses) was associated with a very rapid resolution of the haemangioma and the baby was healthy at follow-up. Although hepatic angiomas are not uncommon in the neonatal period, the association with hydrops is a rare finding.

Influence of goserelin depot therapy on epidermal growth factor receptor expression in pelvic endometriosis.

We have studied epidermal growth factor (EGF) receptor expression in endometrium and in endometriotic implants, testing a group of 36 women before and after a 4-month gonadotropin-releasing hormone (GnRH) analog (GnRH-a) goserelin depot treatment. Each woman underwent laparoscopy twice. At the initial laparoscopy, before starting treatment, the disease was staged according to the American Fertility Society (AFS) classification and biopsies of endometriotic implants were undertaken. The follow-up laparoscopy was performed within 5 weeks of the last GnRH-a administration. Biopsies were taken from areas of previously noted disease, both visually persistent and visually free of disease. At the time of each laparoscopy, photographs of all areas of disease were taken. Specimens of eutopic endometrium were collected from each patient at the time of laparoscopy by a Novak curette. Endometrial and endometriotic samples were processed for immunohistochemical detection of EGF receptor, using anti-EGF receptor monoclonal antibody Ab-3. After treatment, the marked improvement of AFS score was associated with a dramatic reduction of EGF receptor immunostaining, but the exact meaning of this finding is still not completely understood. The dramatic reduction of EGF receptor expression in eutopic and ectopic endometrium samples after treatment is not obviously related to the hypoestrogenism induced by the drug. It has been suggested that steroid hormones and EGF play a role in regulation of EGF receptor expression, so that drugs such as goserelin depot could act directly at local peripheral level influencing the EGF receptor expression via the production of its ligand.

[Retrospective study of postoperative infectious morbidity following cesarean section]. / Studio retrospettivo della morbilità infettiva postoperatoria nel taglio cesareo.

The increase of cesarean sections produced more postoperative infections. Several authors assessed the effectiveness of chemioantibiotic prophylaxis to reduce the postoperative infective morbidity. Although the family of antibiotics more frequently used is that of cephalosporin, the best single agent has not been found yet. The aim of our study, made in the Department of Obstetrics and Gynecology of University of Naples "Federico II", is to propose a retrospective analysis concerning the incidence of cesarean section (CS), the postoperative infective morbidity and the employment of antibiotic prophylaxis. Our sample is a group of 13285 pregnant women, 3171 (23.9%) of these patients underwent to CS from 1st January 1985 to 31st December 1994. The group of 3171 women was divided in two subgroups, the first of 2748 patients un-derwent to antibiotic prophylaxis, the second of 423 was untreated due to their previous experience of allergy towards antibiotics or because there was no evidence of risk factors. The women we treated with antibiotics underwent a three days prophylactic therapy with cefazolin or ampicillin soon after the CS. The incidence of infective complications had a 21.2% rate over a total of 3171 women. Endometritis was the most common infectious complication following cesarean delivery. The rate was 53.3% in the case of primary cesarean section and 52.3% in the case of iterative cesarean section. The use of antibiotic prophylaxis gave us the opportunity to reduce the postoperative morbidity in the primary CS (23.4%) as well in the iterative CS (16.6%). On the contrary the untreated group had an infective incidence with a 33.8% rate in the case of primary CS and with a 27.4% rate in the case of iterative CS. Our opinion is that the administration of antibiotics as cefazolin and ampicillin is able to reduce in a significant way the incidence of postoperative infective morbidity as well the period of hospitalization.

EGF/EGF-R system and benign breast disease during and following the treatment of gynaecological pathologies with an analogue of LH-RH.

Clinical and pathological changes of the mammary gland have been studied in 64 women affected by symptomatic Benign Breast Disease (BBD) coexisting with endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They were evaluated clinically and ultrasonographically before and after treatment to find possible changes of BBD as well as of endometriosis or uterine leiomyomata. Mammary biopsies were performed before and after treatment in all the patients to study the changes of EGF-R expression. Results showed that clinical improvement is accompanied with a reduction of EGF-R expression.

[Progress in tomodensitometry. Applications in cancerology]. / Progrès en tomodensitométrie. Applications en cancérologie.

Since 1992, spiral CT scanners replace conventional CT units in radiology departments. In the first part of this paper, we present some technical considerations concerning spiral CT (continuous rotation and emission of the source-detector; continuous translation of the patient at a constant rate through the gantry), as well as advantages and limitations of volumic acquisition. The main advantages can be summerized as: reduction of the acquisition time, optimization of contrast enhancement with intravenous opacification, and post processing allowing retrospective creation of overlapping images, multiplanar reconstructions, and 3-D reconstructions. Spiral CT improves lesions detection and characterization. Disadvantages are due to contrast media injection and radiation exposure. Then we describe clinical applications in the carcinologic field concerning pharyngo-laryngeal tumors, bronchogenic carcinoma, mediastinal tumors, pulmonary nodules, sub-diaphragmatic tumors. However, tumors of brain, spine, bone, and soft tissue are better explorated with MRI. Authors conclude on the future improvements of spiral CT.

Desogestrel versus gestodene in oral contraceptives: influence on the clinical and histomorphological features of benign breast disease.

Forty-four female volunteers asking for oral contraception, affected by symptomatic benign breast disease (BBD) were evaluated to compare the effects on mastalgia and breast nodularity of two different low dose oral contraceptives (OCs), containing 20 micrograms [corrected] ethinylestradiol + 150 micrograms desogestrel (EE+D) and 30 micrograms ethinylestradiol + 75 micrograms gestodene (EE+G), respectively. Physical examination, bilateral thermography, X-ray and/or ultrasonography of breast, and needle and screw-needle biopsies of mammary tissue were performed in all patients before OCs administration and after six cycles of treatment. OCs administration caused an overall improvement of mastalgia in 53%. Breast nodularity improved only in 8% of patients in both groups. Epithelial tissue modifications in mammary biopsies were observed, with involutive and/or secretory histomorphological and ultrastructural changes, frequently coexisting in different areas of the same breast.

PIP: In Italy, researchers compared data on 22 women who used the low-dose oral contraceptive (OC) containing 20 mcg ethinyl estradiol and 150 mcg desogestrel (EE+D) with data on 22 other women who used the low-dose OC containing 30 mcg ethinyl estradiol and 75 mcg gestodene (EE+G) to determine the pharmacological effects of the 2 OCs on women affected by mastalgia and breast nodularity. Clinicians performed physical exams, bilateral thermography, X-ray and/or ultrasonography of breast and needle and screw-needle biopsies of mammary tissue before OC administration and after 6 cycles of OC treatment. An overall improvement of mastalgia and breast nodularity occurred in 53% and 8% of all patients, respectively. There were no significant differences between groups. Among EE+D treated women, a marked secretory attitude in breast epithelial cells occurred, probably due to a prominent progestin effect. Both OCs increased the number of cytoplasmatic organules and intraluminal secretory material without any apparent increase of cell proliferation. The observed involutive and/or secretory histomorphological and ultrastructural changes often occurred in different areas of the same breast. These results suggest that low dose OC use by women affected by benign breast disease improves mastalgia but not breast nodularity.

Effect of multidose intracorporeal injection and audiovisual sexual stimulation in vasculogenic impotence.

Erections are inhibited by sympathetic stimulation. Anxiety or psychologic inhibition may produce abnormal response during impotence workup. The use of intracorporeal alpha blockers (phentolamine) and audiovisual sexual stimulation (AVSS) has been used to decrease sympathetic outflow and enhance erectile response. Thirty-three patients with suspected vasculogenic impotence were studied. They underwent pulsed Doppler ultrasound (PDUS) with multiple doses of tri-mix (mix of papaverine, phentolamine, and prostaglandin E1). AVSS was applied after maximal response to tri-mix. Seventeen patients (51.5%) responded to multidose with grade IV or V erection. When AVSS was started, 5 more patients responded, and 7 upgraded to grade V with overall response of 40 percent. AVSS can augment the in-office response to pharmacologic testing above that obtained by "maximal" pharmacologic dosing, thereby increasing the sensitivity and specificity of the test.

Potentiation of drug-induced erection with audiovisual sexual stimulation.

Twenty-five patients underwent audiovisual sexual stimulation (AVSS) after pharmacologically-induced erection. Grade of erection and cavernosal blood flow were assessed after intracorporeal (IC) injection of TRI-MIX or prostaglandin E1, and then after AVSS, using pulsed Doppler ultrasonography (PDUS). After IC injection, 5 patients had a Grade II erection, 8 had Grade III, 10 had Grade IV, and 2 had Grade V. There was an increase in peak arterial flow and arterial diameter which corresponded with the grade of erection obtained. After addition of AVSS, 56.5 percent of patients experienced improved erection. The improvement from Grade III to IV in 13 percent is especially significant because it showed the attainment of adequate erection when IC injection alone failed. Penile blood flow improved among AVSS responders but not in nonresponders. AVSS may enhance pharmacologically-induced erection and may improve the diagnostic accuracy of PDUS.

Skeletal muscle is a primary site of insulin resistance in essential hypertension.

To determine the contribution of skeletal muscle to the insulin resistance of essential hypertension, insulin-stimulated forearm glucose uptake was quantitated in 12 control (age, 32 +/- 3 years) and 12 hypertensive subjects (age, 36 +/- 2 years) using the forearm perfusion technique. Peripheral insulin levels were raised acutely (approximately 60 microU/mL), while blood glucose concentration was clamped at its basal value (90 mg/dL) by a variable glucose infusion. During insulin stimulation, whole body glucose uptake was lower in hypertensive (4.5 +/- .3 mg.kg-1.min-1) than in normal subjects (5.8 +/- .4 mg.kg-1.min-1, P less than .05). Similarly, the amount of glucose taken up by the forearm was markedly reduced in the hypertensive (5.3 +/- .91 mg.L-1.min-1) compared with the control group (8.7 +/- 1.1 mg.L-1.min-1). No appreciable difference was observed as to forearm blood flow (39 +/- 4 mL.L-1.min-1 and 37 +/- 5 mL.L-1.min-1) in hypertensive patients. These results indicate that skeletal muscle is a major site of insulin resistance in essential hypertension and that this defect is independent of muscle perfusion.

Carnitine improves peripheral glucose disposal in non-insulin-dependent diabetic patients.

To investigate the effects of carnitine on insulin sensitivity in non-insulin-dependent diabetes, insulin-mediated glucose disposal was measured in nine diabetic patients (age 54 +/- 3 years, BMI 27 +/- 1 kg/mq) during a primed (3 mmol) constant (1.7 mumol/min) intravenous infusion of carnitine. In control experiments, the same patients received saline instead of carnitine. Plasma glucose concentration was maintained constant at the level of 100 mg/dl during both studies while plasma insulin was raised to a plateau of 60 microU/ml. Despite similar insulin levels, whole-body glucose utilization was higher with carnitine (4.05 +/- 0.37 mg/kg/min) than saline infusion (3.52 +/- 0.36). Blood lactate concentrations were similar in the basal state and decreased significantly during carnitine infusion (P less than 0.05-0.005), whereas it remained substantially unchanged during saline infusion. Plasma FFA decreased to a similar level (0.1 mmol/l) in both studies. We conclude that an acute carnitine administration is able to improve insulin sensitivity in NIDDM patients. The lactate data suggest that this effect may at least in part be mediated by carnitine activation of pyruvate dehydrogenase.

Dual mechanism of insulin action on human skeletal muscle: identification of an indirect component not mediated by FFA.

To determine whether insulin action on human skeletal muscle is entirely accounted for by a direct effect of insulin per se, we quantitated forearm glucose uptake (FGU) in two groups of normal subjects under conditions of identical forearm tissue insulinization (approximately 90 microU/ml) induced by means of systemic (group I) or intrabrachial insulin infusion (group II). With this approach, a difference of FGU between the two groups is demonstrative of the operation of indirect mechanisms in insulin action. During insulin infusion in group I, euglycemia was maintained by a variable glucose infusion, whereas arterial free fatty acid (FFA) concentration fell below 0.1 mM. In group II, arterial concentrations of both glucose and FFA remained unchanged, indicating that insulin effect was indeed restricted to the forearm tissues. With local insulin administration, FGU reached levels approximately 40% lower than those achieved with systemic insulin infusion (P less than 0.01-0.005). To determine whether this difference could be attributed to the fall in FFA concentration associated with systemic insulinization, FGU was also quantitated during a systemic insulin plus heparin infusion (group III) to maintain FFA at their basal levels. In this condition, insulin-stimulated FGU was not different from that observed in group I. These data demonstrate that 1) insulin action on skeletal muscle glucose disposal is mediated by a direct as well as an indirect component, and 2) the maintenance of basal FFA does not affect insulin-stimulated FGU, indicating that the indirect component of insulin action is mediated by a different mechanism.