Frequency and prognostic value of HLA antigens in osteosarcoma patients

A homogeneous group of 53 Caucasian subjects with high-grade osteosarcoma (OS) was typed for HLA-A and B locus antigens. Although no significant differences in the distribution of these antigens were found in comparison with 425 local controls, a trend towards an increase of HLA-B18 and decrease of HLA-B21 was observed. All the patients underwent amputation plus adjuvant chemotherapy and among the 29 patients with a follow-up longer than one year, 9 out of 10 subjects with HLA-A3 antigens developed metastases within a few months. None of the OS patients had the HLA-A3, B7 haplotype which is present in linkage-disequilibrium in the control population.     

FN14 Signaling Plays a Pathogenic Role in a Mouse Model of Experimental Autoimmune Myocarditis

BackgroundThe pathogenesis of inflammatory cardiomyopathy is affected by the activation of autoimmune-mediated cascades. To study these cascades, we developed an experimental model of troponin I (TnI)-induced autoimmune myocarditis (EAM). One factor playing a pivotal role in the context of autoimmune disorders is the receptor fibroblast growth factor-inducible 14 (FN14). Thus, the impact of FN14 in the development of autoimmune myocarditis was investigated.Methods and ResultsTnI-immunization led to a significantly increased myocardial FN14 mRNA and protein expression in wild-type (wt) mice. To investigate the precise role of FN14 in EAM, FN14 knockout (ko) and wt littermates were immunized with TnI or control buffer. The animals were evaluated for cardiac parameters and indicators of myocardial injury. FN14 deficiency resulted in better cardiac performance, less myocardial inflammation, fibrosis, and cardiac damage. A lower myocardial mRNA expression of inflammatory cytokines and chemokines as well as their receptors could be demonstrated in TnI-immunized FN14ko compared to wt mice also immunized with TnI. Western blot analysis revealed a contribution of nuclear factor kappa-light-chain-enhancer of activated B cells to FN14-induced signaling cascades.ConclusionsIn the pathogenesis of autoimmune myocarditis, the inflammatory response to cardiac injury is attenuated in FN14ko mice. Thus, inhibition of FN14 in patients might represent a novel therapeutic strategy in the treatment of inflammatory cardiomyopathy.     

Cold extremities and difficulties initiating sleep: evidence of co‐morbidity from a random sample of a Swiss urban population

Difficulties initiating sleep (DIS) can frequently occur in psychiatric disorders but also in the general population. The primary vasospastic syndrome is a functional disorder of vascular regulation in otherwise healthy subjects complaining of thermal discomfort from cold extremities (TDCE). Laboratory studies have shown a close relationship between long sleep onset latency and increased distal vasoconstriction in healthy young subjects. Considering these findings, the aims of the Basel Survey were to assess the prevalence rates for DIS and TDCE and to determine whether both symptoms can be associated in the general population. In a random population sample of Basel‐Stadt, 2800 subjects (age: 20–40 years) were requested to complete a questionnaire on sleep behavior and TDCE (response rate: 72.3% in women, n = 1001; 60.0% in men, n = 809). Values of DIS and TDCE were based on questionnaire‐derived scores. In addition, TDCE was externally validated in a separate group of subjects (n = 256) by finger skin temperature measurements—high TDCE values were significantly associated with low finger skin temperature. A total of 31.1% of women and 6.9% of men complain of TDCE. In contrast, prevalence rates of DIS were only slightly higher in women in comparison to men (9.3% versus 6.7%, P < 0.1). Irrespective of gender, each seventh subject complaining of TDCE had concomitant DIS and the relative risk in these subjects was approximately doubled. Therefore, a thermophysiological approach to DIS may be relevant for its differential diagnosis and its treatment.     

Remifentanil in children

Remifentanil has gained the confidence of anesthesiologists and has given a real opportunity to change the way anesthesia is given. It can be considered the ideal opioid despite many obstacles to pediatric use: the condition of ‘off‐label’, the lack of wide randomized clinical trials, and the fear of adverse events because of its high potency. Experiences in the field with this opioid over the years encouraged its use. Use has been associated with N₂0 and volatile agents for general anesthesia and with propofol for total intravenous anesthesia (TIVA). It seems very useful for sedation inside and outside the operating room and in intensive care for both short painful procedures and synchronization with mechanical ventilation. However, its unique pharmacokinetic characteristics causing rapid onset and offset of effect appear unchanged in small children and even in premature neonates and need to be really confirmed by further pharmacokinetic studies. Moreover, the real risks of tolerance and hyperalgesia should be evaluated in the pediatric population. In this review, we go through the newer aspects of this versatile drug that has been proposed as ‘the pediatric anesthetist’s opiate’.     

Dexamethasone in the Treatment of Bronchopulmonary Dysplasia

Benini, F., Rubaltelli, F. F., Griffith, P., Sala, M. and Zorzi, C. (Department of Paediatrics, University of Padova, Italy). Dexamethasone in the treatment of bronchopulmonary dysplasia. Acta Paediatr Scand Suppl 360: 108, 1989.
Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible during the therapy period. Ventilatory parameters were lowered in 3 other newborns. FIO₂, respiratory rate, PIP, and PEEP, assessed before and after dexamethasone administration, decreased in a statistically significant way. Our data confirm the utility of dexamethasone in the extubation in chronically ventilated infants with BPD.