Significant decline in the erythromycin resistance of group A streptococcus isolates at a German paediatric tertiary care centre

Group A streptococcus (GAS) is considered to be a major pathogen of bacterial tonsillopharyngitis in children. Although GAS is generally susceptible to penicillin, macrolides are often used as the second-line treatment. Over the last several decades, the rising macrolide resistance of GAS has been detected in several countries. With the current study, we aimed to determine the development of macrolide resistance at our paediatric centre. From March 2006 to May 2009, 350 GAS isolates were tested for susceptibility to erythromycin, azithromycin, clindamycin, penicillin and cefotaxime. Macrolide-resistant isolates were screened for the presence of genes related to macrolide resistance (mefA, ermB, ermTR, prtF1). In comparison to a prior study at our hospital, the erythromycin resistance rate decreased significantly from 13.6 to 2.6%. This effect may be attributable to a more restrictive use of macrolides in children in our region.     

Vitiligo in children and adolescents: association with thyroid dysfunction

Background The clinical characteristics of vitiligo in children and adolescents with an emphasis on thyroid dysfunction have only been reported in a few studies. Objective The purpose of this study was to examine the characteristics of children and adolescents with vitiligo and compare the incidence of thyroid dysfunction between them and controls without vitiligo at the same age. Methods A retrospective analysis of 324 Korean children and adolescents with vitiligo was performed. The results of thyroid function screening tests in them (n = 254) were compared with controls (n = 122). Results Of the total 324 children and adolescents with vitiligo, vitiligo vulgaris was the most common type (42.3%) and the most commonly involved site was the face (54.6%). A total of 15 of 254 (5.9%) patients screened for thyroid function were diagnosed with thyroid disease (four had Hashimoto’s thyroiditis; two, Graves’ disease; seven, subclinical hypothyroidism; and two, subclinical hyperthyroidism). None of the 50 patients with segmental vitiligo showed any thyroid dysfunction (P = 0.047). There was no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group, in which seven of 122 (5.7%) showed thyroid dysfunction. Conclusion In this study, we demonstrated the characteristics of children and adolescents with vitiligo and also observed no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group.     

Treating Eating Disorders at Higher Levels of Care: Overview and Challenges

Higher levels of care (HLC)—including inpatient hospitalization, residential treatment, partial hospitalization, and intensive outpatient treatment—are frequently utilized within routine care for eating disorders. Despite widespread use, there is limited research evaluating the efficacy of HLC, as well as clinical issues related to care in these settings. This review describes the different levels of care for eating disorders and briefly reviews the most up-to-date guidelines and research regarding how to choose a level of care. In addition, as HLC approaches for ED continue to be developed and refined, pragmatic and conceptual challenges have emerged that provide barriers to clinical efficacy and the execution of high-quality treatment research. This review includes a discussion of various issues specific to HLC, as well as a summary of recent literature addressing them.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

The effect of electric stimulation treatment on the functional rehabilitation of acute geriatric patients with stroke--a preliminary study

The most common neurological damage in acute stroke/cerebrovascular accident (CVA) is a decline in the senso-motor capacities of both the upper and the lower extremities with a more severe injury in the upper ones. Motor improvement of the affected limb can be attained through frequent intensive exercise by electrical stimulation (ES). The objective of this study was to examine the effect of the ES treatment using Handmaster ES device on the functional rehabilitation of elderly patients after acute CVA. Twenty-two elderly with different levels of damage and partial movements in their upper limb joints underwent a 3-week treatment. Nine of them were treated for additional 3-weeks after a 3-week break. After the first 3-week treatment, significant improvements were observed, in all the subjects, in the active range of motion (ROM) of the shoulder and the wrist joints, on manual dexterity tests and on functional independence measure (FIM). After the two periods of treatment the nine subjects exhibited significant improvements in ROM and in manual dexterity. FIM score increased by the same rate after each of the three stages. This preliminary study has proven that the Handmaster treatment can improve the geriatric rehabilitation outcome of elderly patients with senso-motor deficit caused by acute CVA.     

Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry

OBJECTIVE: A Th1/Th2 cytokine imbalance with a predominance of Th1 cytokines has been suggested to be of pathogenetic importance in rheumatoid arthritis (RA). To evaluate the role of Th1/Th2 cytokines in RA, we used intracellular cytokine flow cytometry to determine cytokine profiles of CD4+ and CD8+ T cells in 34 peripheral blood (PB) and 10 synovial fluid (SF) samples from patients with RA. Results were compared with 10 PB samples from healthy controls (HC) and 5 SF samples from patients with non-RA synovitis. METHODS: After stimulating cells with PMA and ionomycin or alternatively with anti-CD3/CD28 in the presence of brefeldin A, intracellular levels of Th1 [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were determined for CD3+CD8- (i.e., CD4+ Th1 and Th2 cells) and CD3+CD8+ (i.e., CD8+ Tc1 and Tc2 cells) T cells. RESULTS: The percentages of CD4+ and CD8+ Th1 and Th2 cytokines producing T cells (PB) were similar in patients with RA and healthy controls (HC), with a clear predominance of Th1 cytokines expressing, T cells. With regard to T cell subsets, IFN-gamma-producing T cells were significantly more frequently detected in the CD8+ subset [CD8+: median 45.1% (RA; p < 0.001), 38.2% (HC; p = 0.009) vs CD4+: 10.8%(RA), 17.0% (HC)]. Conversely, IL-2 was found in a higher percentage of CD4+ T cells [CD4+: median 33.4% (RA), 17.9% (HC) vs CD8+: 23.6% (RA), 12.3% (HC)]. Patients not in disease remission tended to have more IFN-gamma-producing CD8+ and IL-2-producing CD4+ T cells than patients in remission [CD8+: median 45.9% (IFN-gamma) vs 23.0% (IFN-gamma); CD4+: median 34.1% (IL-2) vs 18.2% (IL-2)1. In all PB samples, the proportion of T cells producing the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 did not exceed 2%. Cytokine profiles did not differ between patients receiving immunosuppressive treatment and patients treated only with nonsteroidal antiinflammatory drugs. In comparison to PB, RA SF analysis revealed a significant increase in the percentage of IFN-gamma-producing CD4+ (p < 0.001) and CD8+ T cells (p < 0.001). In addition, the percentage of IL-10-producing CD4+ (p < 0.001) as well as CD8+ T cells (p = 0.001) was significantly elevated in SF. However, production of the other Th2 cytokines (IL-4, IL-5, IL-13) was similar in SF and PB. CONCLUSION: These data indicate similar cytokine profiles of T cells in PB of RA patients and healthy controls, with a strong predominance of Th1 cytokines producing T cells in the CD4+ and CD8+ T cell subset of both groups. PB cytokine profiles did not significantly differ in patients with active and non-active disease or between patients receiving and those not receiving immunosuppressive medication. In SF, the proportion of Th1 and Tcl cells was significantly elevated compared to PB, emphasizing the local importance of these cells for inflammation. CD8+ T cells (Tc1 cells) mainly contributed to the production of IFN-gamma, indicating an underestimated role of this cell subset for local cytokine production. The upregulation of IL-10-producing Th2 and Tc2 cells in SF may reflect an insufficient effort to down-regulate chronic inflammation in the joint. Modifying this cytokine imbalance in the joints may be a promising therapeutic approach in RA.