Fatal asthma in Finnish children and adolescents 1976-1998: validity of death certificates and a clinical description

Several studies show that asthma mortality in children and adolescents increased until the mid-1990s, after which it has slightly decreased worldwide. The objective of this study was to describe the mortality rates of childhood asthma in Finland, and to analyze patient characteristics to identify predisposing factors for fatal asthma exacerbation among children and adolescents during 1976-1998 (2004). All death certificates where asthma or related respiratory tract disease was coded as the underlying cause of death were reviewed for those under 20 years of age. Health care records and autopsy reports were evaluated to validate the cause of death and to identify any predisposing factors. In all, there had been 28 asthma deaths. The validity of the death certificates proved to be good as only 7% were misclassified. Death occurred either in the very young children or adolescents: the median age in the group of <12 years (n = 15) was 3.3 years while the median age in the group of >12 years (n = 13) was 18.1 years. The fatal exacerbations occurred mostly during summer and early autumn. Clinical triggers, recorded for 14/22 patients with available patient records, included respiratory infection, (12) use of ibuprofen despite known allergy (1), and exercise after visiting a horse stable (1). The severity of the disease was discernible in 21 patients: severe in 15, moderate in 5, and mild in 1 patient. Inhaled corticosteroids were not used as maintenance or periodic therapy in 12/22 patients, of whom 4 had died during the 1990s. In conclusion, asthma mortality in Finnish children and adolescents was rare and its incidence remained stable. The validity of the death certificate diagnoses proved to be good. Poor asthma management and non or undertreatment with inhaled corticosteroids were risk factors for fatal asthma.     

When children tell stories: developmental considerations

Although psychoanalysts welcome children's story creations in the clinical setting, psychoanalytic investigators have given them limited attention. This author examined stories that 40 children, aged 8 to 14, narrated to the Thematic Apperception Test blank card presented in psychological evaluation. The stories depicted playful use of reality as a new development; specific dynamic factors influencing thematic content; humor in latency and self-referencing in (pre-)adolescence as age-specific characteristics. The findings further our understanding of conscious fantasy.     

Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage – a pilot study

Objective The pharmacokinetics of nimodipine following enteral administration in the early phase after subarachnoid haemorrhage (SAH) has not been described. If a sufficient absorption could be achieved with enterally administered nimodipine, this would be more feasible dosage form and result in a significant reduction in pharmaceutical costs given that the parenteral formulation of nimodipine currently used is tenfold more expensive than the enteral formulation. Methods This was a pilot study in which 17 patients with aneurysmal SAH were randomly assigned to receive nimodipine within 24 h after initial bleeding either as an 60 mg tablet/suspension at 4-h intervals, or as a continuous intravenous infusion of 2 mg/h. Serum nimodipine concentrations were measured during the 4 h following the first dose, and at 24 and 72 h on a validated gas chromatography mass spectrometer (GC-MS). Results Nimodipine AUC values (expressed in μg min/ml) were lower in the eight SAH patients receiving enteral nimodipine [AUC_0–4 range: 0.13–5.4 (median: 0.32); AUC_24–28 range: 0.16–6.1 (0.71); AUC_72–76 range: 0.47–20.6 (1.9)] than in the nine patients receiving a continuous intravenous infusion of nimodipine [AUC_0–4 range: 2.4–4.9 (3.4), p = 0.059; AUC_24–28 range: 4.7–10.3 (7.3), p = 0.001; AUC_72–76 range: 3.4–8.6 (6.9), p = 0.001]. In three of five good-grade SAH patients receiving nimodipine tablets the AUC values were comparable to those of the intravenous administration, but in two good-grade patients with tablets and in all three poor-grade (Hunt&Hess, grade IV) SAH patients receiving the suspension, the rate and extent of nimodipine absorption was negligible. Conclusion This pilot study indicates that the rate and extent of nimopidine absorption following enteral administration in some acute SAH patients could be negligible, and this may particularly be the case in patients with a decreased level of consciousness.     

Identification of sensitizing diethyleneglycol maleate in a two-component polyester cement

Unsaturated polyester (UP) cement caused allergic contact dermatitis in car repair work. The resin was a condensate of polyols and maleic anhydride with reactive solvent, auxiliary substances, and inorganic reinforcement substances. To identify the causative chemicals, the cement was tested on a sensitized patient. For analysis, samples of the resin were eluted with acetone and eluted with hexane to precipitate inorganic material and large polyester molecules. The eluate was evaporated. The remainder, dissolved in acetone, was separated into fractions on silica plates by thin layer chromatography (TLC). On the developed (hexane/chloroform, 15/85) plates, 20 bands were obtained under UV-light at 254 nm. Samples of the bands were scraped and used for patch testing. The scraping at a retention factor (Rf) of 0.24 caused a skin reaction. The bands at this retention were removed from six plates, combined, eluted with acetone and purified again by TLC. The purified fraction mixed in petrolatum in the dilution series was used for conclusive patch testing on the patient. An allergic reaction was induced at down to 0.003% wt/wt. According to MS and IR analyses, the isolated compound was diethyleneglycol maleate (DEGM, MW204). In addition to the resin part, the sanding dust also contained this monomer.     

Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis

OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS: Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION: Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.     

L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. α(1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.     

Radioimmunoassay of aescine, a mixture of triterpene glycosides

A radioimmunoassay (RIA) has been developed for the determination of picogram amounts of aescine, an anti-inflammatory and anti-oedematous glycoside mixture from unpurified extracts of Aesculus hippocastanum. Practically no interference is observed for various potentially crossreacting compounds. This RIA covers the range 100 pg-50 ng, within which acceptable accuracy and precision are obtained.     

Season of tumor surgery in relation to deaths among brain tumor patients: does sunlight and month of surgery play a role in brain tumor deaths?

The objective of this study is to investigate the effect at the season of the time of surgery on the survival of brain tumor patients. The population studied consisted of 101 patients (39 males and 62 females), gathered from a geographically large area in northern Finland (from 64°N to 70°N), aged between 20 and 82 years, with a solitary primary brain tumor treated surgically at the Oulu Clinic for Neurosurgery, Oulu University Hospital. The distribution of tumor surgery dates and mean hours of sunshine hours was analyzed by bimonthly periods. When comparing the proportion of deceased patients of all patients operated in each bimonthly period, a significant bimonthly peak in deaths was found in patients operated during the period of February to March (ratio 1.7, 95% CI 1.1–2.3). More than half of the patients who died during the peak period had grade III–IV gliomas. In 40% of the cases, the surgery time of deceased brain tumor patients occurred in the bimonthly period following the four darkest months of the year with the lowest amount of sunshine in northern Finland. The relation of low vitamin D level in the etiology and course of the disease as well as in treatment settings deserves further study.     

Antimicrobial resistance of invasive pneumococci in Finland in 1999-2000

The resistance patterns and macrolide resistance mechanisms of 910 Finnish invasive pneumococci isolated during 1999 and 2000 were studied. Macrolide resistance was detected in 6.9% of isolates. Penicillin resistance was detected in 1.5% of isolates, and penicillin intermediate resistance was detected in 4.0% of isolates. Active macrolide efflux, mediated by the mef(A) gene, was the most common macrolide resistance mechanism. Four macrolide-resistant isolates had mutations in rRNA or ribosomal protein L22.