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.     

Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects

Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0±10/12 years) with a history of respiratory tract, auditory and skin infections, low pi a sin.i levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molten les, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn ⁺⁺/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologicalty before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment, The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school utiendance after zinc supplementation wore recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness in phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS, This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.     

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’.     

Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters

ABSTRACT. The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.     

Immune Dysfunction in Primary Biliary Cirrhosis

In a previous study we observed that after in vitro treatment with indomethacin, lymphocyte response to phytohaemagglutinin (PHA) in primary biliary cirrhosis (PBC) patients was higher than that of controls. We know that indomethacin also inhibits prostanoid production, and thus in the present work we directly measured prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production by mononuclear cells and monocytes from 12 PBC patients, 11 control subjects, and three control disease patients (alcoholic cirrhosis, AC). PHA-stimulated enriched monocytes from PBC patients produced approximately threefold more PGE2 (after 48 h of culture) than did normal and AC monocytes (P less than 0.05). TXB2 production was similar in all groups studied. We also made cultures in which PBC-purified lymphocytes proliferated better than PBC mononuclear cells (i.e. lymphocytes plus monocytes). Thus, a monocyte population producing PGE2 could be responsible, at least in part, for the hyporesponsiveness to PHA observed in PBC patients.     

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.