Macrophage migration inhibitory factor—A potential diagnostic tool in severe burn injuries?

Serum macrophage migration inhibitory factor (MIF) and procalcitonin (PCT) concentrations as well as leucocyte numbers were evaluated in a retrospective study with 23 patients with severe burn injuries. The MIF and PCT concentrations as well as the number of leucocytes (LEU) were monitored over a period of 5 days. The total body surface area (TBSA) and sepsis-related organ failure assessment (SOFA) scores were also evaluated. The MIF, PCT concentrations and leucocyte counts were profoundly increased in all patients with severe burn wounds. At the time of admission into the intensive care unit, no significant differences were observed for the MIF and PCT levels between patients with a TBSA < 60% (Group 1) and patients with a TBSA > 60% (Group 2). After 48 h, however, the MIF and PCT levels reached very high levels in a subgroup of the patients, whereas these levels became normal again in other subgroups. The group of patients with a TBSA > 60% was, therefore, subdivided in three groups (subgroups 2a–c). The MIF and PCT data pairs in these subgroups appeared to correlate in an inhomogeneous manner. These levels in the subgroup 2a (i.e., lethal within 5 days) were strongly elevated over those observed in Group 1 (TBSA < 60%) and highly increased concentrations of both MIF and PCT correlated with lethal outcome. The combined determination of MIF and PCT might, therefore, be useful to discriminate between post-burn inflammation and systemic inflammatory response syndrome (SIRS) or sepsis with lethal outcome.     

Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity.

Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to substantial antidepressant effects in the majority of prior clinical studies. As effect sizes and stimulation conditions have varied greatly, controversy persists regarding effective stimulation parameters (e.g. intensity, frequency, localization). In the present controlled study, we investigated whether the antidepressant efficacy of rTMS may be related to the stimulation intensity applied. Thirty-one patients suffering from a pharmacotherapy-resistant major depressive episode were randomly assigned to three treatment groups receiving rTMS at different stimulation intensities: (1) intensity at the individual motor threshold (MT); (2) 90% subthreshold intensity; and (3) low intensity of standard sham rTMS. Each patient underwent 10 sessions of 10 Hz rTMS with 1500 stimuli/day over the left dorsolateral prefrontal cortex. Improvement of depressive symptoms after rTMS significantly increased with stimulation intensity across the three groups. A 30% to 33% reduction of baseline depression scores was observed after rTMS at MT intensity. Similarly, groups differed significantly regarding the clinical course after rTMS with the lowest number of antidepressant interventions and the shortest hospital stay in the MT intensity group. These findings support the hypothesis of a relationship between stimulation intensity of rTMS and its antidepressant efficacy.     

Skeletal Muscle Tremor and the Influence of Adrenergic Drugs

Physiologic postural skeletal muscle tremor is enhanced by beta2 receptor agonists such as those used in the treatment of asthma. This is a peripheral response rather than one occurring at the central nervous system level. It is greatest when drugs are administered by the oral or parenteral routes, and is the most important dose-limiting factor for oral administration. Clinically important tremor is minimal after aerosolized administration of clinically recommended doses of aerosolized beta₂ receptor agonists, but can be significant when larger doses are administered. Sympathomimetic drugs which can selectively stimulate airway beta₂ receptors, as opposed to skeletal muscle beta2 receptors, do not currently exist. Combining orally administered beta2 agents with theophylline potentiates the effects on muscle tremor. There does not seem to be a clinical advantage, in terms of reduced side effects such as muscle tremor, to combining “small doses” of oral beta agonists and theophylline as opposed to using either agent alone in optimal doses. Tolerance to the tremoregenic effects of beta2 agonists appears to occur when these agents are administered on a chronic basis. Thus, there may be some rationale for beginning oral beta agonists initially with lower doses and progressively increasing to full doses over a period of days to weeks.     

Postoperative Radiotherapy in the Treatment of Ewing Tumors: Influence of the Interval between Surgery and Radiotherapy

Background: The impact of the timing of postoperative irradiation was evaluated in patients with Ewing tumors who received postoperative radiation. Patients and Methods: 153 patients treated in the CESS 86 and EICESS 92 trials were evaluated in a retrospective analysis. They received surgery and postoperative irradiation as local treatment modalities. In 46 patients, postoperative irradiation was started within 60 days after surgery, in 107 patients after more than 60 days. A median dose of 45 Gy was administered. The median follow-up was 70 months. Results: There was no substantial difference between the two groups concerning risk factors for local failure and survival. The local control rate after 5 years was 98% in the group with early onset of radiation and 92% in the group with later onset (n. s.). There is no difference in event free survival between the two groups (both 64% after 5 years). If the cutpoint of the onset of postoperative irradiation was chosen after 90 days, there was no difference in local control or event free survival. Conclusions: Patients with early onset of postoperative irradiation show a trend for improved local control compared to patients with a later onset; the difference is statistically not significant. This trend has no influence on survival. Hintergrund: Der Einfluss des Beginns der postoperativen Strahlentherapie wurde bei Patienten mit Ewing-Tumoren evaluiert, die in den Studien CESS 86 und EICESS 92 behandelt wurden. Patienten und Methode: 153 Patienten aus den Studien CESS 86 und EICESS 92 wurden in einer retrospektiven Auswertung analysiert. Die Lokaltherapie bestand aus einer Resektion und einer postoperativen Bestrahlung. Bei 46 Patienten wurde die postoperative Bestrahlung innerhalb von 60 Tagen nach der Operation begonnen, bei 107 Patienten später. Die mediane Nachbeobachtungszeit betrug 70 Monate. Ergebnisse: Zwischen beiden Gruppen gab es keine wesentliche Unterschiede bzgl. Risikofaktoren für ein Lokalrezidiv und für das Überleben. Die lokale Kontrollrate nach 5 Jahren war 98% in der Gruppe mit frühzeitigem Beginn und 92% in der Gruppe mit späteren Beginn der Radiotherapie (n. s.). Es gab keinen Unterschied im ereignisfreien Überleben zwischen beiden Gruppen (beide 64% nach 5 Jahren). Wenn 90 Tage als Grenze für den Beginn der postoperativen Behandlung gewählt wurde, konnte kein Unterschied in der lokalen Kontrolle und im ereignisfreien Überleben festgestellt werden. Schlussfolgerungen: Patienten mit einem frühen Beginn der postoperativen Bestrahlung zeigten eine tendenziell bessere lokale Kontrollrate; der Unterschied ist statistisch nicht signifikant. Dieser Trend hat keinen Einfluss auf das Überleben.