Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.

PURPOSE: Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. METHODS: In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. RESULTS: We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). CONCLUSION: Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.

Supporting the improvement of air quality management practices: The "FAIRMODE pilot" activity.

This paper presents the first outcomes of the "FAIRMODE pilot" activity, aiming at improving the way in which air quality models are used in the frame of the European "Air Quality Directive". Member States may use modelling, combined with measurements, to "assess" current levels of air quality and estimate future air quality under different scenarios. In case of current and potential exceedances of the Directive limit values, it is also requested that they "plan" and implement emission reductions measures to avoid future exceedances. In both "assessment" and "planning", air quality models can and should be used; but to do so, the used modelling chain has to be fit-for-purpose and properly checked and verified. FAIRMODE has developed in the recent years a suite of methodologies and tools to check if emission inventories, model performance, source apportionment techniques and planning activities are fit-for-purpose. Within the "FAIRMODE pilot", these tools are used and tested by regional/local authorities, with the two-fold objective of improving management practices at regional/local scale, and providing valuable feedback to the FAIRMODE community. Results and lessons learnt from this activity are presented in this paper, as a showcase that can potentially benefit other authorities in charge of air quality assessment and planning.

Asymmetric laterality of Chiari type I malformation in patients with non-syndromic single-suture craniosynostosis.

BACKGROUND: Chiari type I malformation is a frequent incidental finding commonly associated with craniosynostosis. However, there seems to be a paucity of literature concerning the asymmetry of tonsillar herniation in patients with non-syndromic single-suture craniosynostosis. METHODS: To study the asymmetry in this cohort, measurements of the right and left tonsils were made from sagittal images from both pre-operative and post-operative images from 11 patients with non-syndromic single-suture craniosynostosis. RESULTS: Pre-operatively, the mean difference between the caudal descent of all tonsils ranged from 0 to 7 mm, with a mean difference between sides of 2.45 mm. In three cases, cerebellar tonsils were symmetrically herniated. Post-operatively, the mean difference between caudal descent of all tonsils ranged from 0 to 4 mm, with a mean difference between sides of 1.45 mm. Four were symmetrically herniated. In patients with non-syndromic single-suture craniosynostosis, the tonsillar herniation is asymmetric in the majority of cases. CONCLUSIONS: Asymmetry of cerebellar tonsil herniation is a frequent finding in this cohort. The right tonsil is more inferiorly located in majority of cases, with predominance to the synostotic suture side in asymmetric craniosynostosis cases.

Morphometric comparison of foramen magnum in non-syndromic craniosynostosis patients with or without Chiari I malformation.

BACKGROUND: In order to compare the morphometry of foramen magnum (FM) in a matched-pair study, in children with non-syndromic craniosynostosis with and without Chiari I malformation (CMI), both brain magnetic resonance (MRI) and multidetector computed tomography (MDCT) images were utilized. METHODS: Brain MR images were retrieved from the Helsinki University Hospital Picture Archiving and Communications System to identify patients with CMI during 1.1.2004 to 31.3.2009. Age-, gender-, and craniosynostosis-matched controls were retrieved from the same cohort. Morphometric analysis of FM was carried out. RESULTS: Seven patients with non-syndromic craniosynostosis with CMI were recorded. In CMI patients, the absolute anteroposterior length was 33.4 mm as compared to 36.7 mm in controls (p = 0.023). The mean width was 28.1 and 29.9 mm (p = 0.29), and the cross-sectional area was 654.1 and 764.9 mm(2) (p = 0.11) in CMI and controls, respectively. In CMI patients, the relative anteroposterior length of the FM was, on average, 91 % of the control's measurements. On average, the width was 95 % and the cross-sectional area was 88 % of the control's results. CONCLUSIONS: In pediatric non-syndromic craniosynostosis patients, a statistically significant reduced anteroposterior diameter of the FM is found in patients with an adjacent CMI as compared to their age-, gender-, and type-matched controls of craniosynostosis.

The evolution of cerebellar tonsillar herniation after cranial vault remodeling surgery.

PURPOSE: We sought to examine the pre- and postoperative changes of cerebellar tonsillar herniation by MR imaging in asymptomatic pediatric patients with nonsyndromic, single-suture craniosynostosis (N-SSSC), who underwent cranial vault remodeling surgery without suboccipital decompression. We required cerebellar tonsillar herniation through foramen magnum ≥3 mm for Chiari type I malformation (CMI). We hypothesized that the increase of intracranial volume by cranial vault remodeling would correct the asymptomatic CMI. METHODS: We identified 9 patients among 121 N-SSSC children undergoing craniofacial surgery from January 2004 to October 2010 with CMI. However, two of them were excluded from the study due to missing postoperative MR images. In the final study population, six were males, five were scaphocephalic, while two were diagnosed with coronal synostosis. RESULTS: In four of the cases, the CMI was decreased in postoperative MR imaging varying from 6 to 12 mm. In three cases, the herniation remained stable. The median change of cerebellar tonsillar herniation was -6.5 mm. CONCLUSIONS: We conclude that asymptomatic patients with existing CMI may benefit from cranial vault remodeling surgery alone increasing the intracranial volume.

Rupatadine 10 mg in the treatment of immediate mosquito-bite allergy.

BACKGROUND: People frequently experience wealing and delayed papules from mosquito bites. Wealing is mediated by antisaliva IgE antibodies and histamine. Rupatadine is a new antihistamine effective in allergic rhinitis and urticaria, but the effect on mosquito-bite allergy is not known. OBJECTIVE: To determine the effectiveness of rupatadine in inmediate mosquito-bite allergy-confirmed adult patients. METHODS: A double-blind, placebo-controlled, cross-over study was performed with rupatadine 10 mg and matched placebo in 30 mosquito-bite-sensitive adults. The mean age was 37 years and the subjects had suffered from harmful mosquito bites for a mean of 15 years. Either rupatadine or placebo was taken at 08:00 am for 4 days, followed by a 5 day wash out period and then alternative treatment was given for 4 days. On day 3, in both drug periods the subjects received two Aedes aegypti mosquito-bites on the forearm. The size of lesions and intensity of pruritus [visual analogue scale (VAS)] were measured after 15 min bite reaction. RESULTS: Twenty-six subjects were analysed for efficacy. The size of the 15 min bite reaction under placebo was of 106 mm2 and under rupatadine, of 55 mm2. This is a significant decrease (48%; P=0.0003). The accompanying pruritus decreased from 60 (VAS; median) under placebo to 47.5 under rupatadine, which also is a significant (P=0.019) difference. There was no significant (P=0.263) difference in adverse events under rupatadine and placebo. CONCLUSION: The present placebo-controlled study in mosquito-bite-sensitive adults shows that rupatadine 10 mg prophylactically given is an effective treatment for the mosquito-bite wealing and skin pruritus.

Brain anomalies in 121 children with non-syndromic single suture craniosynostosis by MR imaging.

INTRODUCTION: The aim of this study was to evaluate prevalence of intracranial abnormalities in children with non-syndromic single suture craniosynostosis scheduled for cranial vault remodelling surgery using pre-operative magnetic resonance imaging. PATIENTS AND METHODS: A retrospective analysis of brain magnetic resonance imaging studies of 129 non-syndromic single suture craniosynostosis children undergoing craniofacial surgery between January, 2004-October, 2010 was conducted. Statistical analysis was performed for child, maternal and sibling related predisposing factors for abnormal brain magnetic resonance imaging findings. The mean age of these 121 patients at the time of imaging was 21.6 months. The majority, 78% were males and 74% of the patients were scaphocephalic. RESULTS: In 18 (15%) patients abnormal brain findings were noted. The most common finding was Chiari 1 malformation in 11 (9%). Chiari 1 malformation comprised over half (61%) of the brain anomalies identified. None of these findings required any additional surgical procedures. None of the statistical analysis reached statistical significance. CONCLUSIONS: Brain anomalies in connection with non-syndromic single suture craniosynostosis patients seem to be a coincidental event. We did not establish any specific craniosynostosis form to be regularly associated with abnormal brain magnetic resonance imaging findings. The routine use of pre-operative magnetic resonance imaging in non-syndromic single suture craniosynostosis patients seems to be of limited value in the search for associated intracranial malformations necessitating additional interventions.

Comparison of cetirizine, ebastine and loratadine in the treatment of immediate mosquito-bite allergy.

BACKGROUND: People frequently experience whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva immunoglobulin (Ig)E antibodies and histamine. Cetirizine, ebastine and loratadine have earlier shown effects on mosquito-bite reactions but no comparative studies exist. METHODS: A double-blind, placebo-controlled, cross-over study was performed with cetirizine 10 mg, ebastine 10 mg and loratadine 10 mg in 29 mosquito-bite-sensitive adults exposed to Aedes aegypti mosquito-bites. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and 2, 6 and 24 h. RESULTS: Cetirizine and ebastine, but not loratadine, decreased significantly the size of whealing (P < 0.01) and accompanying pruritus (P < 0.001) compared to placebo. Cetirizine was most effective on pruritus but caused more often sedation than ebastine or loratadine. The delayed bite symptoms remained too faint for any statistical comparison. CONCLUSION: This comparative study in mosquito-bite-sensitive adults shows that cetirizine and ebastine decrease significantly whealing and accompanying pruritus, and that cetirizine seems to be the most effective against pruritus.

Loratadine in the treatment of mosquito-bite-sensitive children.

BACKGROUND: Children frequently experience harmful whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva IgE antibodies and histamine, but the effect of antihistamines on mosquito-bite symptoms has not been evaluated in children. METHODS: The effect of loratadine (0.3 mg/kg) was examined in 28 mosquito-bite-sensitive children (aged 2-11 years). The double-blind, placebo-controlled, crossover study was performed with exposure to Aedes aegypti laboratory mosquitoes. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and at 2, 6, and 24 h. RESULTS: Loratadine decreased the size of the wheals by 45% (P < 0.001, 25 children) and accompanying pruritus by 78% (P = 0.011, 12 children) at 15 min compared to placebo. The size of the 24-h delayed bite lesion also decreased significantly (P = 0.004), but there was no change at 2 or 6 h. Loratadine was well tolerated and no marked side-effects were recorded. CONCLUSIONS: This study in children shows that prophylactically given loratadine decreases significantly the whealing and pruritus caused by mosquito bites and also reduces the size of the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.

Treatment of mosquito bites with ebastine: a field trial.

Wealing and pruritic, long-lasting papules are a common nuisance from mosquito bites. Antihistamines can be expected to decrease wealing, but their effect on the delayed bite symptoms needs to be elucidated. We studied the effect of ebastine in 28 mosquito-bite sensitive adult subjects exposed to Aedes communis bites in the field. Ebastine 20 mg and placebo were given for 4 days in a cross-over fashion, and the size of the bite lesion and the intensity of pruritus (visual analogue scale) were measured at 15 min and 2, 6 and 24 h after the bites. Ebastine decreased significantly (p <0.001) the size of the bite lesion and pruritus at 15 min. Ebastine also had a significant effect (p<0.01) on pruritus at 2 and 24 h, and this effect was highly significant when the measurements at all 4 time points were pooled. Five patients (18%) on ebastine, but none on placebo, experienced sedation (ns). The present field study shows that ebastine 20 mg given prophylactically is effective against immediate mosquito bite symptoms, and that it also significantly decreases pruritus associated with the delayed bite papules.

Correlation of polyamine and growth responses to N1,N11-diethylnorspermine in primary fetal fibroblasts derived from transgenic mice overexpressing spermidine/spermine N1-acetyltransferase.

A recently generated transgenic mouse line having activated polyamine catabolism due to systemic overexpression of spermidine/spermine N1-acetyltransferase (SSAT) was used to isolate primary fetal fibroblasts as a means to further elucidate the cellular consequences of activated polyamine catabolism. Basal levels of SSAT activity and steady-state mRNA in the transgenic fibroblasts were about approximately 20- and approximately 40-fold higher than in non-transgenic fibroblasts. Consistent with activated polyamine catabolism, there was an overaccumulation of putrescine and N1-acetylspermidine and a decrease in spermidine and spermine pools. Treatment with the polyamine analogue N1,N11-diethylnorspermine (DENSPM) increased SSAT activity in the transgenic fibroblasts approximately 380-fold, whereas mRNA increased only approximately 3-fold, indicating post-mRNA regulation. SSAT activity in the nontransgenic fibroblasts increased approximately 200-fold. By Western blot, enzyme protein was found to increase approximately 46 times higher in the treated transgenic fibroblasts than non-transgenic fibroblasts: a value comparable to 36-fold differential in enzyme activity. With DENSPM treatment, spermidine pools were more rapidly depleted in the transgenic fibroblasts than in nontransgenic fibroblasts. Similarly, transgenic fibroblasts were much more sensitive to DENSPM-induced growth inhibition. This was not diminished by co-treatment with an inhibitor of polyamine oxidase, suggesting that growth inhibition was due to polyamine depletion per se as opposed to oxidative stress. Since the two fibroblasts were genetically identical except for the transgene, the various metabolic and growth response differences are directly attributable to overexpression of SSAT.

Poor prognosis of gallbladder cancer persists regardless of improved diagnostic methods. Incidence and results of surgery during 20 years in Helsinki.

BACKGROUND AND AIMS: The ominous prognosis of primary gallbladder cancer is well-known. This study assesses whether the prognosis has improved, and whether the substantial development in the radiologic imaging techniques is reflected in the survival of these patients. MATERIAL AND METHODS: The series consisted of 122 patients operated on for primary cancer in the gallbladder in the Helsinki City area between 1970 and 1990. RESULTS: The mean age of the patients was 68.6 years and did not change during the period, but there was a significant proportional increase in male patients. Only 2% of patients had a localized disease at the time of diagnosis, and there was no improvement in the diagnostic sensitivity during the observation period. Yet, the number of unexpected postoperative cancer diagnoses increased from 4% to 15% during the two decades. The primary mortality decreased from 21% to 13%, the one-year survival increased from 7% to 13%, whereas the five-year survival remained unchanged. CONCLUSIONS: During the past two decades the frequency of surgery for primary gallbladder cancer has increased significantly among males in the Helsinki City area. Regardless of the improved immediate survival the long-term survival has remained poor. The marked development in radiologic techniques is not reflected in the prognosis of these patients. Even under conditions in which the potential for the diagnosis of a malignant gallbladder disease is available, the opportunities for radical surgery are not utilized maximally, which is a cause for concern.

Effect of cetirizine on the inflammatory cells in mosquito bites.

BACKGROUND: Mosquito bites frequently cause wealing and delayed papules which appear within a few hours after the bites and may persist for several days. Cetirizine is an effective drug against mosquito bites by decreasing wealing and also the size and pruritus of the delayed bite papules. OBJECTIVES: To characterize inflammatory cells in the delayed mosquito-bite lesions, and to study the effect of cetirizine on the inflammatory cell response. METHODS: Twenty-six mosquito-bite sensitive subjects received cetirizine 20 mg (14 subjects) or placebo (12 subjects) in a double-blind fashion. Aedes aegypti-bites were given on a forearm and serial punch biopsies were taken at 2-, 6- and 24h after the bite exposure. Eosinophils, neutrophils, mast cells, mononuclear cells and T- helper (CD4+) and suppressor (CD8+) lymphocytes were counted from dermal infiltrates. RESULTS: Eosinophils and neutrophils were found already in 2-h bite lesions. Moreover, the number of mononuclear and CD4+ cells increased significantly (P < 0.01) from 2- to 24-h bite lesions. Unexpectedly, the overall numbers of eosinophils (P < 0.05), mononuclear cells (P < 0.01) and CD4+ cells (P < 0.01) were significantly higher in the cetirizine-treated subjects compared with the placebo-treated subjects. CONCLUSIONS: The results suggest that the inflammatory cell response in the delayed mosquito-bite lesions is similar to that occurring in allergic late-phase responses, i.e. an early influx of eosinophils, neutrophils and subsequent accumalation of CD4+ lymphocytes. The reason for the high numbers of eosinophils and CD4+ cells in the cetirizine-treated subjects is not known.

Immunocytochemical localization of glucocorticoid receptor in rat skin.

The aim of the present study was to map immunohistochemically the distribution of the glucocorticoid receptor (GR) in rat skin. Nuclear GR-like immunoreactivity (LI) was found in both epidermis and dermis. In the epidermis, the basal cell layer showed an intense immunoreaction; the lower part of the spinous layer was also labelled. In the dermis, the fibroblasts as well as the sweat glands, sebocytes and adipocytes were GR-immunoreactive (IR). In the root sheath of the hair follicle the staining was most intensive in the outer layer. The endothelial cells comprising the smooth muscle cells of the blood vessels, as well as the arrector pili muscle, showed GR-LI. In the peripheral nerves, the immunoreaction was localized to the nuclei of the Schwann cells and in the perineurial fibroblasts. Mast cells did not show nuclear GR-LI. Based on our immunocytochemical findings that several cell types of the skin are GR-IR, the variable physiological and pharmacological effects of glucocorticoids are easier to understand.

Treatment of mosquito bites with cetirizine.

Eighteen adult subjects sensitive to mosquito bites participated in a double-blind, placebo-controlled study with 10 mg cetirizine. The drug was given prophylactically and the subjects were then exposed to bites of Aedes communis mosquitoes in the field. Bite lesions were measured and pruritus was scored with a visual analogue scale at 15 min, 60 min, 12 hr and 24 hr. Cetirizine significantly decreased immediate wealing and pruritus and, interestingly, also had a clear effect on the delayed 12 hr and 24 hr bite papules and pruritus. The diameter of a 15 min mosquito-bite weal was 10.1 +/- 10.4 mm (mean +/- s.d.) with the placebo and 5.9 +/- 5.9 mm with cetirizine treatment (P < 0.05). The 15 min pruritus scores were 36.0 +/- 25.2 and 11.2 +/- 13.2 (P < 0.001), respectively. The diameter of the 24 hr mosquito-bite lesion was 12.6 +/- 21.9 mm with the placebo and 7.4 +/- 16.1 mm with cetirizine treatment (P < 0.01). The 24 hr pruritus scores were 18.9 +/- 25.5 and 6.6 +/- 14.8 (P < 0.01), respectively. These results indicate that, in mosquito-sensitive subjects, prophylactically administered cetirizine is an effective drug against both immediate and delayed mosquito-bite symptoms.

Synaptosomal accumulation of intracerebrally injected amino acids.

The distribution of the labels of [35S]taurine, [3H]lysine, [14C]glutamate and [14C]norleucine in mouse brain subcellular fractions was followed after intracerebral injection in vivo. [35S]taurine, [3H]lysine and [14C]glutamate and its metabolites accumulated in the nerve terminals, lysine and glutamate also occurring in the synaptic vesicles, while remained mainly in soluble synaptoplasm [14C] nor leucine penetrated the brain cell membranes slowly, but was still bound to the synaptic vesicles to a greater extent than taurine.

Amino acids in the synaptic vesicle fraction from calf brain: content, uptake and metabolism.

A synaptic vesicle fraction was prepared from calf brain cortex, containing 10 identified amino acids and two unidentified ninhydrin-positive compounds, one of which is apparently a peptide. The most plentiful amino acids were taurine (1.8 nmol/g original tissue), glutamic acid (1.8), serine (0.9), aspartic acid (0.8) and GABA (0.8); the others identified were cysteic acid (or cysteinesulphinic acid), glutamine, alanine, glycine and lysine. The unknown peptide occurred in a high concentration (about 16 alanine equivalents/g), and contained mainly aspartic acid and serine. Cysteic acid (or cysteinesulphinic acid) also occurred in relatively high amounts, but its peak contained acid-labile impurities. The influx of [14C]glutamate into the vesicles took place by means of non-saturable migration, while two saturable systems having very similar properties were dominant only at low glutamate concentrations. Influx constants for these quantitatively low uptake systems were Km, 34 and 92 micrometer, and Vmax, 33 and 49 nmol/min/g obtained by v versus v/S plot. Almost the same values were also obtained by a 1/v versus 1/S plot. GAD and GABA-T activities in the vesicles were only 1/200th of those in the synaptosomes.