The natural history of allergy: the development of new sensitizations in asthmatic children

Allergy is an important risk factor for asthma in children as most of asthmatic children are sensitized. The aim of the study was to investigate the natural course of sensitizations in a group of children (340) at the onset of asthmatic symptoms. We subdivided children in three groups depending on the age at first visit (3-7-11 years) and followed them for 4 years. All children underwent three visits, each including skin prick test, every two years. In the 3-year age group (n = 133), 59% of children were sensitized at first visit, but the percentage increase to 88% at third visit. When looking only at allergic children at first visit (261), we demonstrated that polysensitization became higher than monosensitization since the age of 11. Analysis of sensitization distribution over the time revealed that house dust mites were prominent from the age of 3 years. Parietaria and grass pollens as well as olive pollen significantly increased, particularly during the 4-year follow-up in the 7-year group. Analysis of sensitization score demonstrated that the age range from 3 to 11 is at high risk to polysensitization. In conclusion, this study provides evidence that sensitization is frequent in asthmatic children, polysensitization represents the natural history of allergy and the type of immune response should appear different for each allergen.     

Improved bronchodilator effect of deep inhalation after allergen avoidance in asthmatic children

BACKGROUND: In healthy adults and children, deep inhalation (DI) is able to reverse induced bronchoconstriction. This ability is impaired in asthma, but the reasons are still to be elucidated. OBJECTIVES: This study investigated whether the bronchodilator effect of DI during methacholine-induced bronchoconstriction can be improved by allergen avoidance in asthmatic children, and its relationship with airway inflammation. METHODS: The effect of DI on methacholine-induced bronchoconstriction was studied at the beginning and the end of a 3-month allergen avoidance period at high altitude in 14 allergic asthmatic children who had severe asthma attacks. Changes in airway caliber were inferred from the respiratory resistance (Rrs) measured by a forced oscillation technique. Results were related to the percentage of eosinophils in induced sputum and compared with those obtained in 9 age-matched nonasthmatic children. RESULTS: In asthmatic subjects, DI had no significant effect on methacholine-induced increase in Rrs before (P=.62) but significantly reversed it after (P <.01) allergen avoidance. However, the ability of DI to reverse a methacholine-induced increase in Rrs tended to remain less in asthmatic than nonasthmatic children even after allergen avoidance (P=.05). In the asthmatic children, the percentage of eosinophils in induced sputum was decreased at the end of the allergen avoidance period (P <.001), without any significant correlation between sputum eosinophils and airway responsiveness to methacholine or effect of DI. CONCLUSION: A short period of allergen avoidance may improve the ability of DI to reverse induced bronchoconstriction in some asthmatic children. This effect is associated, yet not correlated, with a reduction in airway inflammation.     

The role of intraoperative nerve monitoring in tracheal surgery: 20-year experience with 110 cases

Purpose

To determine the utility of intraoperative nerve monitoring (IONM) during tracheal resection or slide tracheoplasty to prevent recurrent laryngeal nerve injury.

Methods

110 patients underwent tracheal resection or tracheoplasty between 1997 and 2016. During the first 10-year period, IONM was not used while during the second 10-year period, IONM was used. 49 patients had surgery without IONM while 61 had surgery with IONM. During the post-operative period, patients with nerve injury were compared to determine if significant difference existed between the two modalities.

Results

In patients who had surgery without IONM, 7 (14.2%) patients were found to have compromised nerve function whereas 8 (13.1%) patients in the group with IONM had nerve injury. 3 patients regained function in the first group while four regained function in the second. A Fisher’s exact test was run on the entire cohort and the difference in vocal fold injury was not found to be statistically significant (p > 0.05).

Conclusion

Based on this single surgeon experience, there may be no protective benefit with the use of IONM during tracheal surgery.

     

Four-year follow-up of larger-diameter implants placed in fresh extraction sockets using a resorbable membrane or a resorbable alloplastic material

PURPOSE: The aim of this randomized study was to evaluate and compare the long-term success rates of cylindric, screw-type titanium implants with a larger diameter (5.9 mm) that were placed in fresh extraction sockets in association with resorbable bone substitutes or a resorbable membrane. MATERIALS AND METHODS: Eighty-three partially edentulous adult patients, selected from among those treated in 1997 and 1998 at the San Raffaele Institute in whom 1 or more implants had been placed into fresh posterior mandibular or maxillary sockets, were included in the study. A total of 111 implants were placed, 36 in mandibles and 75 in maxillae. Fifty-six implants were placed in combination with resorbable hydroxyapatite (HA group) and 55 with a resorbable membrane (MR group). Intraoral radiographs and follow-up examinations, including verification of implant stability via the Periotest, were carried out at second-stage surgery 3, 6, 9, and 12 months later; and then annually up to 4 years after placement of the definitive restoration. The radiographic examination was conducted by means of a standardized procedure to verify osseointegration. RESULTS: There was 100% attendance at the follow-up examination after 4 years. At second-stage surgery, which was performed after 4 to 6 months' healing time, none of the implants showed any signs of mobility, peri-implantitis, or bone loss. Two implants failed in the MR group, one at 3 months and one at 9 months after placement; 1 implant failed in the HA group at 4 months after placement. After 4 years, the implant success rate was 97.3% (108 of 111 implants were considered successful). The success rate did not differ significantly between the HA group (98.2%) and the MR group (96.4%). DISCUSSION: The use of larger-diameter implants served to minimize the anatomic discrepancies that would have evolved when substituting a molar with a standard-diameter implant. According to the accepted criteria for success, the 5-year success rate should be at least 85%; therefore both methods may be considered satisfactory. CONCLUSION: Implants placed in combination with a resorbable allogeneic material or with a resorbable membrane provided predictable long-term results when restored with a fixed partial denture.     

Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity

A novel class of combretastatins, modified at A-ring or both A- and B-rings, mainly by replacement with benzofuran or benzo[b]thiophene, were synthesized. The new heterocombretastatins showed good cytotoxic activity on BMEC and H-460 cell lines. The aminocombretastatin 9f potently inhibits cell growth of BMEC and combretastatin-resistant HT-29 cell lines, with potential interest to treat colon carcinoma. Heterocombretastatins 9a,b inhibit tubulin polymerization similarly to CA-4 by having a binding to colchicine site five times stronger.     

Aeromonas veronii biovar veronii and sepsis-infrequent complication of biliary drainage placement: A case report

BACKGROUND Aeromonas species are uncommon pathogens in biliary sepsis and cause substantial mortality in patients with impaired hepatobiliary function. Asia has the highest incidence of infection from Aeromonas,whereas cases in the west are rare.CASE SUMMARY We report the case of a 64-year-old woman with advanced pancreatic cancer and jaundice who manifested fever,abdominal pain,severe thrombocytopenia,anemia and kidney failure following the insertion of a percutaneous transhepatic biliary drainage. Blood culture results revealed the presence of Aeromonas veronii biovar veronii(A. veronii biovar veronii). After antibiotic therapy and transfusions,the life-threatening clinical conditions of the patient improved and she was discharged.CONCLUSION This was a rare case of infection,probably the first to be reported in West countries,caused by A. veronii biovar veronii following biliary drainage. A finding of Aeromonas must alert clinician to the possibility of severe sepsis.     

Neurons rely on glucose rather than astrocytic lactate during stimulation

Brain metabolism increases during stimulation, but this increase does not affect all energy metabolism equally. Briefly after stimulation, there is a local increase in cerebral blood flow and in glucose uptake, but a smaller increase in oxygen uptake. This indicates that temporarily the rate of glycolysis is faster than the rate of oxidative metabolism, with a corresponding temporary increase in lactate production. This minireview discusses the long-standing controversy about which cell type, neurons or astrocytes, are involved in this increased aerobic glycolysis. Recent biosensor studies measuring metabolic changes in neurons, in acute brain slices or in vivo, are placed in the context of other data bearing on this question. The most direct measurements indicate that, although both neurons and astrocytes may increase glycolysis after stimulation, neurons do not rely on import of astrocytic-produced lactate, and instead they increase their own glycolytic rate and become net exporters of lactate. This temporary increase in neuronal glycolysis may provide rapid energy to meet the acute energy demands of neurons.     

Folding versus charge: understanding selective target recognition by the thrombin aptamers

The use of nucleic acids as drugs represents a consistently growing approach. Different therapeutical strategies take advantage of the biological and biophysical properties of DNA and RNA to properly modulate activity of selected targets. A peculiar characteristic of these molecules is their structural flexibility which allows them to assume distinct foldings depending upon their sequence and/or environment. During the last twenty years this has led to the theoretical and experimental development of oligonucleotide aptamers, short sequences which can recognize a target with specificity and affinity comparable to antibodies. A leading example is represented by the Thrombin aptamer (15fTBA), a 15-mer DNA selected by its high affinity for the exosite I (fibrinogen binding site) of the coagulation factor. The very stable protein-DNA complex formation is the result of complementarities between the two macromolecules promoted by the aptamer sequence and folding as well as of electrostatic interactions generated by the charge balance at the binding site/s. Here, we investigated the relative role of these contributions and their involvement in defining the biological properties of the resulting complex. Thus we compared the Thrombin binding and inhibition properties of TBA to those of unrelated single stranded oligonucleotides. Additionally, the differences between the two protein exosites were assessed by using 29hTBA, a longer (29-mer) aptamer known to bind exosite II (heparin binding site). A subtle balance of aptamer folding and sequence is shown to cooperate with charge density for effective and selective recognition of exosite I or exosite II by TBAs.     

SIRT1 signaling as potential modulator of skeletal muscle diseases

Skeletal muscle diseases heavily impair the strength and the movement of patients. Muscles loose their adaptive capacity, undergoing atrophy or wasting, due to a number of pathological insults. Metabolic changes, such as those occurring during aging, contribute to the progressive reduction of myofiber size and decline of skeletal muscle performance that is typically observed in the elderly. The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 has been involved in the protection against metabolic disorders, against cancers and in the enhancement of life span. Here we discuss the current evidence placing SIRT1 at the crossroad between energy homeostasis, fiber strength, and regeneration from damage in the skeletal muscle. Furthermore, we underline how cell type specific targeting of SIRT1 could be beneficial in the treatment of skeletal muscle diseases.     

Posttraumatic enophthalmos: etiology, principles of reconstruction, and correction

Enophthalmos is defined as a backward, and usually downward, displacement of the globe into the bony orbit. In posttraumatic enophthalmos, the mechanisms that determine globe position are: 1) the enlargement of the orbital cavity; 2) the herniation of orbital fat into the maxillary sinus; and 3) fat atrophy, loss of ligament support, and scar contracture. The aim of this article is to analyze the strategies to prevent enophthalmos and to correct late posttraumatic enophthalmos. In this study, 80 patients (52 cases of orbitozygomatic fractures and 28 late posttraumatic enophthalmos) were treated between January 1998 and January 2005. Fracture reduction in primary enophthalmos was performed. In enophthalmos as sequelae, the treatment consisted of orbital reconstruction in combination with bone grafts harvested from calvaria, iliac crest, and/or orbital osteotomies. In some cases, biomaterials were also used. All these techniques may also be combined depending on the severity of enophthalmos. The results were satisfactory in all cases. It is evident that a perfect correction of the deformity is difficult to achieve. Often soft tissue changes limit the aesthetic and morphologic results, despite adequate bony reconstruction.