Leuprolide and triptorelin treatment in children with idiopathic central precocious puberty: an efficacy/tolerability comparison study.

Introduction: Central precocious puberty (CPP) results from premature activation of hypothalamic-pituitary-gonadal axis, with the consequent increase of gonadotropin-releasing hormone (GnRH); GnRH agonists (GnRHa) represent the gold-standard therapy in children with CPP although their use might be responsible for pituitary GnRH receptors down-regulation, that in turn suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH) and blocks of gonadal sex hormones release. The most prescribed GnRHa in the clinical practice are leuprolide and triptorelin, whose use is generally safe and well tolerated; however, mild menopausal-like side effects could appear. The aim of the present study was to investigate and compare the efficacy and tolerability profile of leuprolide and triptorelin in CPP patients. Methods: 110 girls affected by CPP were enrolled in this retrospective study, carried out from 2018 to 2020. The enrolled patients received leuprolide (n = 48) or triptorelin (n = 62). Efficacy was investigated by the means of clinical parameters and radiological changes and side effects were also recorded to evaluate the possible relationship between the two GnRHa treatments and side effects appearance. Results: At baseline triptorelin patients had significantly higher LH and LH peak levels than leuprolide patients, whereas no significant difference in other patient characteristics was observed between the two groups. The leuprolide treatment lasted 971 days [790-1,171 days] while the duration of triptorelin administration was 792 days [760-1,003 days] (p < 0.001). Overall 46 (41.8%) of the studied patients reported mild menopausal-like symptoms: among these 27 were treated with triptorelin and 19 with leuprolide (p = 0.558). Patients treated with triptorelin, or leuprolide showed headache (27.4% vs. 16.7%), mood swings (12.9% vs. 16.7%), increased appetite (12.9% vs. 18.8%) and nausea (1.6% vs. 10.4%) respectively. Moreover, the onset of side effects appearance related to GnRHa therapy significantly reduces with the increase of the initial bone age (p = 0.038). Conclusion: Leuprolide and triptorelin treatment appear to be effective and safe without significant difference between the two drugs in term of efficacy and tolerability, making both good options for treating CPP.

Composition law of κ-entropy for statistically independent systems.

The intriguing and still open question concerning the composition law of κ-entropy S_{κ}(f)=1/2κ∑_{i}(f_{i}^{1-κ}-f_{i}^{1+κ}) with 0<κ<1 and ∑_{i}f_{i}=1 is here reconsidered and solved. It is shown that, for a statistical system described by the probability distribution f={f_{ij}}, made up of two statistically independent subsystems, described through the probability distributions p={p_{i}} and q={q_{j}}, respectively, with f_{ij}=p_{i}q_{j}, the joint entropy S_{κ}(pq) can be obtained starting from the S_{κ}(p) and S_{κ}(q) entropies, and additionally from the entropic functionals S_{κ}(p/e_{κ}) and S_{κ}(q/e_{κ}),e_{κ} being the κ-Napier number. The composition law of the κ-entropy is given in closed form and emerges as a one-parameter generalization of the ordinary additivity law of Boltzmann-Shannon entropy recovered in the κ→0 limit.

Cholesteric-nematic transition in an asymmetric strong-weak anchoring cell.

We discuss the cholesteric-nematic transition induced by an external field in a cell in the shape of a slab of finite thickness whose anchoring energy is infinitely strong on one surface and negligible on the other. The case where the surface orientations of the cholesteric director are parallel in the ground state is considered. In a sample of thickness ℓ, multiple of the natural periodicity of the system Λ, the number of complete twists in the cholesteric liquid crystal is reduced by increasing the strength of the external distorting field. The sequence of the field values for expelling complete twists accumulate as the strength of the field approaches a critical value. Beyond this critical value the system assumes an unwinding configuration going toward a uniform structure, corresponding to nematic phase. Generalization of the results to the weak-weak anchoring cell case is also discussed. In our analysis the anisotropic part of the surface energy is assumed or very large or very small with respect to the total energy per unit surface due to the bulk distortion induced by the magnetic field.

Effect of botulinum toxin antral injection on gastric emptying and weight reduction in obese patients: a pilot study.

BACKGROUND: A potential approach to the treatment of morbid obesity is reduction of gastric emptying to achieve satiety. Botulinum toxin A (Btx-A) is a long-acting inhibitor of acetylcholine-mediated peristalsis, which is mainly responsible for gastric motility. AIM: To investigate whether botulinum toxin A, injected in the antrum of obese patients, delays gastric emptying. METHODS: In a double_blind study, 18 healthy obese subjects (body mass index >30) were randomized into three groups (BTX133, BTX200 and Saline); they received Btx-A133U, Btx-A200U, or saline under endoscopic control. Gastric emptying was tested by scintigraphy before and 10 days after treatment. Body weight variations and appetite sensation were recorded after 5 weeks. RESULTS: Fourteen patients completed the study. The botulinum toxin A-treated groups showed weight reduction, which was not statistically significant. The effects on gastric emptying were variable. Most of the botulinum toxin A treated patients reported a reduced appetite. CONCLUSION: This pilot clinical trial suggests potential activity of botulinum toxin A for the manipulation of appetite.

Thermodynamic equilibrium and its stability for microcanonical systems described by the Sharma-Taneja-Mittal entropy.

It is generally assumed that the thermodynamic stability of equilibrium states is reflected by the concavity of entropy. We inquire, in the microcanonical picture, about the validity of this statement for systems described by the two-parametric entropy S(kappa,r) of Sharma, Taneja, and Mittal. We analyze the "composability" rule for two statistically independent systems A and B, described by the entropy S(kappa,r) with the same set of the deformation parameters. It is shown that, in spite of the concavity of the entropy, the "composability" rule modifies the thermodynamic stability conditions of the equilibrium state. Depending on the values assumed by the deformation parameters, when the relation S(kappa,r)(A union B) > S(kappa,r)(A) + S(kappa,r)(B) holds (superadditive systems), the concavity condition does imply thermodynamics stability. Otherwise, when the relation S(kappa,r)(A union B) < S(kappa,r)(A) + S(kappa,r)(B) holds (subadditive systems), the concavity condition does not imply thermodynamical stability of the equilibrium state.

Canonical quantization of nonlinear many-body systems.

We study the quantization of a classical system of interacting particles obeying a recently proposed kinetic interaction principle (KIP) [G. Kaniadakis, Physica A 296, 405 (2001)]. The KIP fixes the expression of the Fokker-Planck equation describing the kinetic evolution of the system and imposes the form of its entropy. In the framework of canonical quantization, we introduce a class of nonlinear Schrödinger equations (NSEs) with complex nonlinearities, describing, in the mean-field approximation, a system of collectively interacting particles whose underlying kinetics is governed by the KIP. We derive the Ehrenfest relations and discuss the main constants of motion arising in this model. By means of a nonlinear gauge transformation of the third kind, it is shown that in the case of constant diffusion and linear drift, the class of NSEs obeying the KIP is gauge-equivalent to another class of NSEs containing purely real nonlinearities depending only on the field rho=|psi|(2) .

Two-parameter deformations of logarithm, exponential, and entropy: a consistent framework for generalized statistical mechanics.

A consistent generalization of statistical mechanics is obtained by applying the maximum entropy principle to a trace-form entropy and by requiring that physically motivated mathematical properties are preserved. The emerging differential-functional equation yields a two-parameter class of generalized logarithms, from which entropies and power-law distributions follow: these distributions could be relevant in many anomalous systems. Within the specified range of parameters, these entropies possess positivity, continuity, symmetry, expansibility, decisivity, maximality, concavity, and are Lesche stable. The Boltzmann-Shannon entropy and some one-parameter generalized entropies already known belong to this class. These entropies and their distribution functions are compared, and the corresponding deformed algebras are discussed.

Effects of propionyl-L-carnitine topical irrigation in distal ulcerative colitis: a preliminary report.

BACKGROUND/AIMS: To study the tolerability of propionyl-L-carnitine administered as rectal irrigation and its efficacy in improving the clinical picture of distal ulcerative colitis. METHODOLOGY: Ten male subjects (aged 18 to 55 years, with a body mass index ranging from 21 to 25 Kg/m2) with distal ulcerative colitis were treated with propionyl-L-carnitine enemas (6 g in 200 mL physiological solution) twice a day over 120 minutes each. All subjects had a disease activity index from 0 to 1. A clinical, laboratory, endoscopy and biopsy evaluation was performed at baseline and 14 days after treatment. Serum tumor necrosis factor-alpha and interleukin-2 concentration was measured. RESULTS: No side effects were reported by the entire patient population and the clinical conditions remained constant throughout the study period. The disease activity index improved significantly between the beginning and the end of the study in 80% of the patients. Histologic features (mucosal erosion, distortion of crypt architecture, inflammation and lamina propria gap) significantly improved in all treated patients. Serum interleukin-2 levels did not change significantly after propionyl-L-carnitine treatment (respectively: 14.7 +/- 15.8 before vs. 9.9 +/- 13.2 pg/mL), while tumor necrosis factor-alpha levels were undetectable both before and after propionyl-L-carnitine administration. CONCLUSIONS: The topical treatment with a new formulation containing propionyl-L-carnitine seems to be safe and effective in improving the histologic features in patients with inactive or mild ulcerative colitis, as an alternative to conventional therapy.

Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery.

One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease (CHD) risk. A cross-sectional study was designed to randomly assign 79 morbidly obese subjects (27 men and 52 women; age: 30-45 years) either to a diet protocol (20 kcal per kg fat-free mass (FFM); 55% carbohydrates, 30% fat, and 15% proteins) or to malabsorptive surgery (biliopancreatic diversion). Fatness parameters, measured by dual-energy X-ray absorptiometry, lipid profile, insulin, leptin, sex steroid hormones and sex hormone-binding globulin (SHBG) levels were compared at baseline and 1 year after the beginning of the study. The data showed that plasma SHBG levels, but not testosterone levels, correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women. Total leptin levels were significantly lower (P<0.0001) in post-BPD subjects of both sexes compared to dietary treated obese subjects. The logarithm of plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG, but not insulin levels, were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients. The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness. Finally, in obese patients, SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis.

Enteral diet in Crohn's disease. Nutritional and therapeutic implications in patient's management.

Inflammatory bowel diseases (IBD) are often characterized by impairment of nutritional status. Crohn's disease (CD) patients, especially in the active phase of disease, show a reduced body weight, due to the reduction of lipid stores, in spite of lean mass depletion. Fat mass reduction has been correlated to an increased utilization of lipids as fuel substrate. The alterations of nutritional status are able, in turn, to influence, as independent factors, the disease course and patient prognosis. A disease's treatment based only on pharmacologic therapy, especially on corticosteroid use in the active phases, often does not take into account the relevant need for preserving a normal nutritional status. In this connection, enteral nutrition has been shown to be able to improve nutritional status and induce and maintain remission. We present some of the possible mechanisms of efficacy of enteral feeding and some rules to attempt to treat patients with IBD, especially those with Crohn's disease.

Main physiopathologic mechanisms involved in hepatic drug reactions.

The liver has a pivotal role in drug metabolism and hepatic drug reactions are frequent events, accounting for 5% of cases of jaundice or acute hepatitis in the community. The importance of hepatic drug reactions lies not only in their frequency, but also in the great number of molecules that can cause this type of lesions and in their variable gravity. This review will show the main factors implicated in drug metabolism which can explain the different susceptibility in developing hepatic drug reaction, the possibility that it may manifest as a wide spectrum of clinical syndromes or that a single agent may cause more than one lesion (a relevant problem not only for the clinician, but also for the pathologist).

Quantum vortices in systems obeying a generalized exclusion principle.

The paper deals with a planar particle system obeying a generalized exclusion principle (EP) and governed, in the mean field approximation, by a nonlinear Schrödinger equation. We show that the EP involves a mathematically simple and physically transparent mechanism, which allows the genesis of quantum vortices in the system. We obtain in a closed form the shape of the vortices and investigate its main physical properties.

Alterations of nutritional status in the main gastrointestinal pathologies.

An impairment of nutritional status up to real malnutrition can frequently be associated to gastrointestinal diseases. The diseases of the gastrointestinal tract can be divided into five groups: those hampering the nutrient physiological transit (especially neoplastic diseases); those affecting the intestinal mucosa (such as chronic inflammatory bowel disease); those determining intraluminal maldigestion; the hepato-biliary diseases and finally, the diseases of the pancreas. In order to correctly evaluate the nutritional status of an individual, besides the determination of the common biochemical parameters, body composition by direct and indirect techniques and energy metabolism by indirect calorimetry should be measured. Patients affected by Crohn's disease showed a lower fat mass content along with higher lipid oxidation compared to patients affected by ulcerative colitis. Patients with coeliac disease at diagnosis had a reduction in both fat and fat-free mass content along with an increased utilisation of carbohydrates as fuel substrate. There are many factors potentially leading to severe malnutrition in pancreatic diseases, especially in the acute form. Due to the primary role played by the liver in the metabolism of energy substrates, an impaired nutritional status might be commonly found in cirrhotic patients. In this connection, our group reported an increased energy expenditure and lipid oxidation, and an insulin-resistant state in compensated liver cirrhotic patients. These alterations seemed to precede and probably to lead to liver-disease-related malnutrition.

Wasting in gastrointestinal tract cancers: clinical and etiologic aspects.

One of the major complications found in patients affected by malignancy of the gastrointestinal tract is represented by an alteration of nutritional status, up to real cachexia. The factors responsible for the severe nutritional deficiencies are: metabolic alterations, which involve carbohydrate, lipid and protein metabolism; the reduced availability of nutritional substrates, due to neoplastic growth that, by expanding locally or destroying the affected organ, determines alterations of deglutition, digestion and food absorption; the effects of surgical therapy, radiotherapy and chemotherapy, which are able to cause temporary or permanent nutritional deficiencies; the effects of immunological mediators, and above all of tumor necrosis factor-alpha (TNF-alpha). In fact, TNF-alpha is considered the main mediator of cancer cachexia as it is responsible for different metabolic alterations, both directly and by the activation of other mediators, such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF). In addition, a negative energy balance in cancer patients could occur as a consequence of increased energy requirements. In this connection, patients with different neoplasia localisation, show high or within the normal range energy expenditure values. These data indicate that the increase in energy metabolism is not likely to represent the main determining factor in neoplastic cachexia. In conclusion, since patients affected by malignancy of the gastrointestinal tract showed a reduction in body weight, fat and fat-free mass, accurate evaluation of nutritional status should be useful in the management and follow-up of these patients.

Bilateral posterior scleritis.

PURPOSE: To describe an unusual presentation of posterior scleritis in a healthy young patient. METHOD: We reviewed the medical record of 21-year-old man for clinical presentation, course, and ancillary studies. RESULTS: The healthy patient had a painless, bilateral posterior scleritis that presented with a combination of circumscribed fundus masses and exudative macular detachment. On fluorescein angiography, different hyper-fluorescent patterns characterized the two manifestations of posterior scleritis. An ultrasound confirmed the scleral thickening. Fundoscopic abnormalities resolved with oral prednisone. CONCLUSION: Pain is not always present in this disease. A combination of exudative macular detachment and circumscribed fundus masses can be a form of presentation in posterior scleritis.