Erwiderung auf die Bemerkung von Dr. Scholtz zu meiner Arbeit: Wann können wir die Gonorrhoe als geheilt ansehen?

Ohne Zusammenfassung     

Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages

Whereas local microglial cells of the CNS rapidly respond to injury, little is known about the functional role of resident macrophages of the peripheral nervous system in nerve pathology. Using bone marrow chimeric rats, we recently identified individual resident endoneurial macrophages that rapidly became activated after nerve injury. However, the extent of local macrophage activation and its quantitative contribution to the total macrophage response is unknown. We now have created chimeric mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated wild-type mice, allowing easy differentiation and quantification of hematogenous and resident endoneurial macrophages. After sciatic nerve crush injury, both GFP(-) and GFP(+) resident macrophages, the latter having undergone physiological turnover from the blood before injury, rapidly underwent morphological alterations and increased in number. Proliferating GFP(-) and GFP(+) resident macrophages were abundant and peaked 3 days after injury. A major lesion-induced influx of hematogenous macrophages with a disproportionate increase of GFP(+) macrophages was not observed until Day 4. Throughout all time points examined, GFP(-) resident macrophages were strikingly frequent, reaching maximum numbers 9.5-fold above baseline. There was also a notable proportion of GFP(-) resident endoneurial macrophages phagocytosing myelin and expressing major histocompatibility complex class II. Our results demonstrate for the first time that the rapid response of resident endoneurial macrophages to nerve injury is quantitatively important and that local macrophages contribute significantly to the total endoneurial macrophage pool during Wallerian degeneration.     

Cattle density and Shiga toxin-producing Escherichia coli infection in Germany: increased risk for most but not all serogroups

Shiga toxin-producing Escherichia coli (STEC) cause severe gastroenteritis and life-threatening hemolytic-uremic syndrome. For STEC of serogroup O157, association between disease incidence and cattle contact has been established in some countries. For other (non-O157) serogroups, however, accounting for approximately 80% of notified STEC gastroenteritis in Germany, the role of cattle in human infection is less clear. For example, an association of non-O157 STEC infection and cattle density has not been investigated. The aim of this study was thus to investigate a potential association between STEC incidence and cattle density in Germany, with special attention to the non-O157 serogroups. We modeled district-level incidence of notified human STEC cases in relation to cattle density, utilizing German notification data from 2001 through 2003. Cattle numbers came from the national "Proof of Origin and Information Database for Animals." A Bayesian Poisson regression model was used, incorporating independent, as well as spatially correlated, district-level random effects into the analysis. We analyzed 3216 German STEC cases. Cattle density was positively associated with overall STEC incidence. The risk for STEC infection increased by 68% per 100 additional cattle/km(2). The magnitude of the risk estimates differed by serogroup and was greatest for O111. A positive association was found for all major disease-causing serogroups (O26, O103, O111, O128, O145, O157) except O91. The association with serogroup O26 (lowest median age of patients) was only borderline significant. Residual variation indicates that additional factors not under study may also be of importance, and that they may be serogroup- and region-specific, too. In conclusion, this study suggests that living in a cattle-raising region appears to imply risk not only for STEC O157, but also for most non-O157 serogroups. Furthermore, the varying magnitude of this risk and the residual variation found for different serogroups indicate that risk profiles for human STEC infection may be serogroup-specific. This needs to be taken into account in risk factor studies for non-O157 STEC, ideally by reporting risks separately by serogroup.     

A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors

Positively selected CD34(+) hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO(+) HLA-DR(+), whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA(+) naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of gammadelta T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.     

Effects of ankle–foot braces on medial gastrocnemius morphometrics and gait in children with cerebral palsy

PurposeIn children with cerebral palsy (CP), braces are used to counteract progressive joint and muscle contracture and improve function. We examined the effects of positional ankle–foot braces on contracture of the medial gastrocnemius (MG) and gait in children with CP while referencing to typically developing children.MethodsSeventeen independently ambulant children with CP and calf muscle contracture (age 10.4 ± 3.0y) and 17 untreated typically developing peers (age 9.5 ± 2.6y) participated. Children with CP were analysed before and 16 ± 4 weeks after ankle–foot bracing. MG muscle belly length and thickness, tendon and fascicle length, as well as their extensibility were captured by 2D ultrasound and 3D motion capturing during passive, manually applied stretches. In addition, 3D gait analysis was conducted.ResultsPrior to bracing, the MG muscle–tendon unit in children with CP was 22 % less extensible. At matched amounts of muscle–tendon unit stretch, the muscle belly and fascicles in CP were 7 % and 14 % shorter while the tendon was 11 % longer. Spastic fascicles displayed 32 % less extensibility than controls. Brace wear increased passive dorsiflexion primarily with the knees flexed. During gait, children walked faster and foot lift in swing improved. MG muscle belly and tendon length showed little change, but fascicles further shortened (−11 %) and muscle thickness (−8 %) decreased.ConclusionsUse of ankle–foot braces improves function but may lead to a loss of sarcomeres in series, which could explain the shortened fascicles. To potentially induce gastrocnemius muscle growth, braces may also need to extend the knee or complementary training may be necessary to offset the immobilizing effects of braces.     

Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the long-term clinical efficacy of inhaled iloprost as first-line vasodilator mono-therapy in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: Seventy-six IPAH patients were prospectively identified and treated with inhaled iloprost. Clinical, haemodynamic, and exercise parameters were obtained at baseline, after 3 and 12 months of therapy and yearly thereafter. Four endpoints were prospectively defined as follows: (i) death, (ii) transplantation, (iii) switch to intravenous (i.v.) therapy, or (iv) addition of or switch to other active oral therapy. During follow-up (535+/-61 days), 11 patients died, six were transplanted, 25 were switched to i.v. prostanoids, 16 received additional or other oral therapy, and 12 patients discontinued iloprost inhalation for other reasons. Event-free survival at 3, 12, 24, 36, 48, and 60 months was 81, 53, 29, 20, 17 and 13%, respectively. Among haemodynamic and exercise parameters, mixed venous oxygen saturation (P<0.001), right atrial pressure (P<0.001), and peak oxygen uptake (P=0.002) were associated with event-free survival. CONCLUSION: In this study, only a minority of patients could be stabilized with inhaled iloprost mono-therapy during a follow-up period of up to 5 years. In the presence of multiple treatment options, chronic iloprost inhalation as mono-therapy appears to have a limited role.     

Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients‘ perspective

Pituitary - While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient...