Local anesthesia in pediatric dermatologic surgery: Evaluation of a patient‐centered approach

Background/Objectives

A few studies have documented the effect of local anesthesia for minor dermatologic surgical procedures on children and their parents. Our objective was to evaluate the psychological effect and global satisfaction of a patient‐centered approach to dermatologic surgery under local anesthesia.

Methods

Two self‐administered questionnaires were used to evaluate the distress and global satisfaction of 388 children who underwent dermatologic surgery under local anesthesia, accompanied by oral and written therapeutic education measures (structured information and a cartoon brochure illustrating the procedure) addressed to children and parents. Distraction techniques were also used during the procedures.

Results

Although 54.5% of patients manifested some degree of fear, all other parameters analyzed (pain, surgery‐related distress, surgical team–patient and –family relationship, global satisfaction) indicated that the procedures resulted in limited distress and that the large majority of children and parents tolerated them well.

Conclusion

Specific measures for therapeutic pediatric patient education may be helpful in limiting discomfort, anxiety, and pain perception linked to procedures performed under local anesthesia. Further controlled studies are required to more precisely assess the benefits of specific therapeutic education measures.     

Static magnetic fields modulate X-ray-induced DNA damage in human glioblastoma primary cells

Although static magnetic fields (SMFs) are used extensively in the occupational and medical fields, few comprehensive studies have investigated their possible genotoxic effect and the findings are controversial. With the advent of magnetic resonance imaging-guided radiation therapy, the potential effects of SMFs on ionizing radiation (IR) have become increasingly important. In this study we focused on the genotoxic effect of 80 mT SMFs, both alone and in combination with (i.e. preceding or following) X-ray (XR) irradiation, on primary glioblastoma cells in culture. The cells were exposed to: (i) SMFs alone; (ii) XRs alone; (iii) XR, with SMFs applied during recovery; (iv) SMFs both before and after XR irradiation. XR-induced DNA damage was analyzed by Single Cell Gel Electrophoresis assay (comet assay) using statistical tools designed to assess the tail DNA (TD) and tail length (TL) as indicators of DNA fragmentation. Mitochondrial membrane potential, known to be affected by IR, was assessed using the JC-1 mitochondrial probe. Our results showed that exposure of cells to 5 Gy of XR irradiation alone led to extensive DNA damage, which was significantly reduced by post-irradiation exposure to SMFs. The XR-induced loss of mitochondrial membrane potential was to a large extent averted by exposure to SMFs. These data suggest that SMFs modulate DNA damage and/or damage repair, possibly through a mechanism that affects mitochondria.     

Fludarabine,ara-C,novantrone and dexamethasone (FAND) in previously treated chronic lymphocytic leukemia patients

BACKGROUND AND OBJECTIVES: The objective of improving the quality of responses of chronic lymphocytic leukemia (CLL) patients has led to the design of protocols that combine fludarabine (FDR) with synergistic drugs. We evaluated the efficacy and toxicity of a schedule that includes fludarabine, ara-C, novantrone and dexamethasone (FAND) for the management of previously treated CLL patients under 60 years old. DESIGN AND METHODS: Thirty-one patients underwent FAND treatment. Twenty-three patients had active disease (relapsed patients: 9; unresponsive to prior therapy: 14). Eight patients had a partial response (PR) to prior therapy and were treated with the aim of further reducing residual disease. The FAND schedule included fludarabine (25 mg/m(2) i.v. days 1-3), ara-C (1 g/m(2) i.v. day 1: 8 patients; days 1-2: 23 patients), novantrone (10 mg/m(2) i.v. day 1) and dexamethasone (20 mg i.v. days 1-3). Infection prophylaxis consisted of fluconazole, acyclovir, trimethoprim/sulfamethoxasole and granulocyte colony-stimulating factor (G-CSF) in the presence of severe neutropenia. RESULTS: A response was observed in 7/14 refractory patients (complete response-CR: 29%), in all 9 relapsed patients (CR: 78%) and in 7/8 patients (CR: 87.5%) treated in PR. Taken together, 18 CRs were obtained and in 14 (78%) this was associated with a flow cytometric remission (CD5+/CD20(weak+) PB lymphocytes: <10%). Severe granulocytopenia occurred after 86 of the 124 administered courses (69%), but only after 10/86 courses (12%) were major infections recorded. In 10/15 mobilized patients (cyclophosphamide + G-CSF: 6 patients; FAND + G-CSF: 9 patients) after FAND > or = 2 x 10(6)/kg CD34+ cells were collected. Nine patients were autografted in CR and showed a longer response duration than the 9 patients in CR who did not receive further therapy after FAND (53 vs 30% at 41 months; p = 0.05). INTERPRETATION AND CONCLUSIONS: FAND associated with extensive infection prophylaxis and G-CSF support is a highly cytoreductive and well-tolerated treatment for CLL patients and in most cases does not hamper subsequent stem cell mobilization.     

23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G

The 23S rRNA A2058G alteration mediates macrolide, lincosamide, and streptogramin B resistance in the bacterial domain and determines the selectivity of macrolide antibiotics for eubacterial ribosomes, as opposed to eukaryotic ribosomes. However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci. We used site-directed mutagenesis of nucleotides within domain V of 23S rRNA to study the molecular basis for this disparity. We show that mutational alteration of the polymorphic 2057-2611 base pair from A-U to G-C in isogenic mutants of Mycobacterium smegmatis significantly affects susceptibility to ketolides but does not influence susceptibility to other macrolide antibiotics. In addition, we provide evidence that the 2057-2611 polymorphism determines the fitness cost of the 23S rRNA A2058G resistance mutation. Supported by structural analysis, our results indicate that polymorphic nucleotides mediate the disparate phenotype of genotypically identical resistance mutations and provide an explanation for the large species differences in the epidemiology of defined drug resistance mutations.     

An analysis of the genetic factors involved in testicular descent in a cohort of 14 male patients with anorchia

Anorchia, or the "vanishing testis syndrome," is characterized by the absence of testis in a 46,XY individual with a male phenotype. The etiology is unknown; however, the familial occurrence of the disease and the association of this phenotype with 46,XY gonadal dysgenesis has led to the suggestion that genetic factors, which play a role in testicular determination, may be involved. Alternatively, exploratory laparoscopy has suggested that anorchia may be caused by a prenatal testicular vascular accident associated with torsion during testicular descent. We screened a cohort of 14 boys with bilateral anorchia for mutations in the Y chromosome-linked testis-determining gene SRY (sex-determining region, Y chromosome); in the gene necessary for correct testicular descent, INSL3; and in the gene of its receptor (LGR8). Mutations in the INSL3 gene and the LGR8 T222P mutation are known to cause cryptorchidism. We confirmed previous reports that mutations in the SRY gene are not associated with anorchia. Although a common polymorphism was identified in the INSL3 gene, no mutations were observed. The recurrent T222P mutation in the LGR8 gene was not found in any of the patients. These data show for the first time a lack of association between genetic factors necessary for correct testicular descent and anorchia.     

Influence of vasostatins, the chromogranin A-derived peptides, on the working heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action

We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1), Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on the mechanical performance of the isolated and perfused working eel (Anguilla anguilla) heart. Under basal conditions, the three peptides decreased stroke volume (SV) and stroke work (SW), thus exerting negative inotropism. The VS-1-mediated negative inotropism was abolished by exposure to inhibitors of either Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine, tetraethylammonium, glibenclamide) channels, while it required an intact endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger, we demonstrated the obligatory role of NO signaling in mediating the vasostatin response. Pretreatment with either a specific inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated inotropism, indicating the cGMP-PKG component as a crucial target of NO signaling. Of note, VS-1 was effective in counteracting the adrenergic (Isoproterenol and Phenylephrine)-mediated positive inotropism. These findings provide the first evidence that vasostatins exert cardiotropic action in fish, thus suggesting their long evolutionary history as well as their species-specific mechanisms of action.