Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child. METHODS: An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. RESULTS AND CONCLUSION: The diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up. Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

[Procedural pain perception of preterm newborn in neonatal intensive care unit: assessment and non-pharmacological approaches]. / Percezione del dolore procedurale del nato pretermine in terapia intensiva neonatale: valutazione e tecniche non farmacologiche d'intervento.

AIM: The aim of this study was to evaluate the reaction to the procedural pain of preterm newborn and to demonstrate the different effectiveness of the two analgesic and not pharmacological techniques of recent clinical acquisition, the use of glucose solution and the sensorial saturation, in order to identify an optimal strategy for the prevention and pain treatment. METHODS: We take a sample of 28 preterm newborns of 30-35 weeks. The subjects are divided in two randomized groups following the kind of analgesia used during the hematic sample from heel: the first group (group A) included 14 subjects, who received glucose solution associated to no nutritive suction; the second group (group B) included 14 subjects who received the sensorial saturation. The symptoms associated with pain at the moment of venous sample are measured through premature infant pain profile (PIPP) scale. RESULTS: Results show that the score was lower in the group treated with sensorial saturation (media 6.52; P<0.001) than in the group treated with glucose (media 13.80; P<0.05). CONCLUSION: The use of "care" techniques (in our case sensorial saturation) ameliorates the quality of life in NICU and reduces the pain threshold perceived by newborn, reducing therefore the exposition to the pain stimulus and the possibility that some consequences due to an inadequate pain treatment in neonatal age could develop.

Serum proteolytic activities and antiproteases in human colorectal carcinoma.

Some proteolytic enzymes, trypsin, cathepsin B, cathepsin D, collagenase, elastase and their inhibitors, API and AMG, in serum of patients with colorectal carcinoma have been evaluated. Twenty patients belonged to stage B of colorectal carcinoma, twenty two patients to stage D (Astler and Coller classification) and a control group of thirty healthy volunteers were evaluated. Except in cathepsin D, patients exhibit higher enzymatic activities than healthy subjects, and both groups have all the proteolytic activities assayed in serum. Patients with disseminated disease have increased cathepsin B and collagenase levels, with a decrease of trypsin activity, showing an increment in API and AMG in sera. However, only the API values were significantly higher in patients with metastases. The coexistence of proteolytic activities in human sera together with their inhibitors is considered as well as the origin of these, tumoral and/or reactive, increments. Cathepsin B levels are raised in colorectal neoplasms and contribute to the destruction of the extracellular matrix and the proliferation of tumoral cells. There is evidence that a relation between collagenase like activity and tumor invasiveness exists. Cathepsin B and collagenase increases agree with the tumoral mass. On the other hand, trypsin decrease in metastatic carcinoma is probably related to the increment of their inhibitors, API and AMG, acute phase reactant proteins.

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador.

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

Analysis of the leaching and toxicity of new amine activators for the curing of acrylic bone cements and composites.

The comparative reactivity of new tertiary amine activators with the basic chemical structure of N,N-dimethyl-4-toluidine, but reduced toxicity, is analysed. The leaching of the amine compounds from cured cements was studied by analysis of the concentration of the corresponding amine in a physiological saline solution after 3 months of immersion, giving lower values for the new amine compounds as compared to N,N-dimethyl-4-toluidine. The acute toxicity was determined by intravenous injection of saline solutions of the corresponding chlorhydrates in mice and the cytotoxicity by the evolution of specific culture media. The results obtained demonstrate a lower acute toxicity and cytotoxicity of the new activators, even with a noticeable antiseptic action, which makes these materials very interesting from a practical point of view as activators of the curing process of acrylic bone cements for orthopaedic surgery and dentistry.

Application of tertiary amines with reduced toxicity to the curing process of acrylic bone cements.

4-Dimethylaminobenzyl alcohol (DMOH) and 4-dimethylaminobenzyl methacrylate (DMMO) were used as the activators in the benzoyl peroxide initiated redox polymerization for the preparation of acrylic bone cement based on poly(methylmethacrylate) beads of different particle size. The residual monomer content of the cured cements was about 2 wt %, independent of the redox system used in the polymerization, indicating that the activating effect of the tertiary aromatic amines DMOH or DMMO was sufficient to reach a polymerization conversion similar to that obtained with the benzoyl peroxide (BPO) N,N-dimethyl-4-toluidine (DMT) system. The BPO/DMOH and BPO/DMMO redox systems provided exotherms of decreasing peak temperature and increasing setting time, and the cured materials presented higher average molecular weight and similar glass transition temperatures in comparison with those obtained when DMT was used as the activator. In addition, these activators are three times less toxic than the classical DMT.

Polymeric drugs derived from ibuprofen with improved antiinflammatory profile.

A new methacrylic monomeric compound bearing Ibuprofen (MIA) and the respective polymethacrylic macromolecular derivative (polyMIA) were evaluated for antiinflammatory properties in order to study their pharmacological activity profile. The macromolecular drug is constituted of Ibuprofen residues linked covalently to a polymethacrylic support, as a side substituent of the repeating unit, by means of a spacer group (p-aminophenoxy) that, in addition, is the most representative metabolite of Paracetamol. The Ibuprofen is slowly released from the polymeric support by hydrolysis of the ester bond in a biological medium. Different antiinflammatory testing methods were used; and the results obtained indicate that the monomeric and polymeric forms display higher potency to inhibit acute inflammatory processes than the traditional Ibuprofen form, even doubling the power of Ibuprofen. In addition, they present higher activity against chronic experimental processes, as well as an excellent antinociceptive behavior to inhibit the pain associated with arthritic diseases. According to previous reports and results presented in this article, we can conclude that the new polymethacrylic structures show higher analgesic, antipiretic, and antiinflammatory activities due to the possible activity of the macromolecular drug as well as to the controlled Ibuprofen release from the macromolecular delivery system. After releasing of the side active residue, a derivate of poly(sodium methacrylate) is formed, which is cleared from the body easily by the normal pathway of kidney metabolism.

[Acute phase reaction after inflammatory injury. Experimental study]. / Reacción de fase aguda tras agresión inflamatoria. Estudio experimental.

It is well known that inflammatory aggression makes important changes in plasma proteins levels. Among all of these proteins, C3 fragment of the complement system and haptoglobin, Acute Phase Reactants Proteins, are considered important mediators of the inflammatory response although their specific behaviour is not completely understood. In this work we have studied the modification of both proteins after an inflammatory aggression, which was experimentally induced in rats, trying to connect their behaviour with the lesion stages. Our data show that the plasmatic level of both proteins is increased during the inflammatory aggression, although haptoglobin level gives a more accurate approach to the local phenomenons which occur in the inflammatory focus. This fact suggests that each acute phase reactant has a certain specificity depending on the kind of aggression suffered by a patient.

[Acute-phase reaction after inflammatory aggression. Experimental study]. / Reacción de fase aguda tras agresión inflamatoria. Estudio experimental.

It is well known that inflammatory aggression makes important changes in plasma proteins levels. Among all of these proteins, C3 fragment of the complement system and haptoglobin, Acute Phase Reactants Proteins, are considered important mediators of the inflammatory response although their specific behaviour is not completely understood. In this work we have studied the modification of both proteins after an inflammatory aggression, which was experimentally induced in rats, trying to connect their behaviour with the lesion stages. Our data show that the plasmatic level of both proteins is increased during the inflammatory aggression, although haptoglobin level gives a more accurate approach to the local phenomenons which occur in the inflammatory focus. This fact suggests that each acute phase reactant has a certain specificity depending on the kind of aggression suffered by a patient.

Thymic factor therapy for herpetic keratitis.

Thirty patients with herpetic keratitis were allocated to a double-blind trial with either local treatment plus placebo (control group) or local treatment plus thymostimulin (TS group). The follow-up at 24 months demonstrated a significant reduction of recurrence rate among patients receiving thymostimulin, along with a significant increase of sheep rosette-forming cells (E rosette). Furthermore, among patients with superficial keratitis, thymostimulin treatment resulted in a significantly quicker corneal re-epithelization than placebo. Thymostimulin seems to be a safe and helpful drug in the management of herpetic keratitis.

Prognosis in Behcet's disease.

A retrospective clinical study made to determine the course and prognosis of the disease in 51 cases of Behçet's disease, with a follow-up of at least one year (average five years, range 1 to 15 years), showed that 45% of the eyes kept visual acuities of 1/10 or less, and 44% 8/10 or better, four years after the onset of the ocular symptoms. Ten years later, some 50% of the eyes had visual acuities of 1/10 or less and 32% had acuities of 8/10 or better. In the group of patients who were treated early with chlorambucil, the eye prognosis was significantly improved.

[Haptoglobin in the biological diagnosis of gastric cancer (author's transl)]. / La haptoglobina en el diagnóstico biológico del cáncer gástrico.

Serum haptoglobin has been determined in a series of 69 patients with metastatic and non-metastatic gastric cancer. In both circumstances a marked increase of haptoglobin levels in comparison to the results in the control group was observed. A significant decrease was noticed in the presence of liver metastasis. Total alpha 2-globulin levels were also high in this patients, but a significant decrease was not observed in cases with liver metastasis. There was no parallelism between the values of haptoglobin and total alpha 2-globulins. The usefulness of these results in the diagnosis and prognosis of gastric cancer is stressed. Radial immunodiffusion using immunoserum anti-haptoglobin 1-1 is the technique of choice.