The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus fumigatus isolates from azole-naive patients in Denmark despite negative findings in the environment.

Azole-resistant Aspergillus fumigatus harboring the TR34/L98H or TR46/Y121F/T289A alterations is increasingly found in Europe and Asia. Here, we present the first clinical cases of TR46/Y121/T289A and three cases of TR34/L98H outside the cystic fibrosis (CF) population in Denmark and the results of environmental surveys. Four patients (2012 to 2014) with 11 A. fumigatus and 4 Rhizomucor pusillus isolates and 239 soil samples (spring 2010 and autumn 2013, respectively) with a total of 113 A. fumigatus isolates were examined. Aspergillus isolates were screened for azole resistance using azole-containing agar. Confirmatory susceptibility testing was done using the EUCAST microbroth dilution EDEF 9.1 reference method. For relevant A. fumigatus isolates, CYP51A sequencing and microsatellite genotyping were performed. Three patients harbored TR34/L98H isolates. Two were azole naive at the time of acquisition and two were coinfected with wild-type A. fumigatus or R. pusillus isolates, complicating and delaying diagnosis. The TR46/Y121F/T289A strain was isolated in 2014 from a lung transplant patient. Genotyping indicated that susceptible and resistant Aspergillus isolates were unrelated and that no transmission between patients occurred. Azole resistance was not detected in any of the 113 soil isolates. TR34/L98H and TR46/Y121F/T289A alterations appear to be emerging in the clinical setting in Denmark and now involve azole-naive patients. Two recent soil-sampling surveys in Denmark were unable to indicate any increased prevalence of azole-resistant A. fumigatus in the environment. These findings further support the demand for real-time susceptibility testing of all clinically relevant isolates and for studies investigating the seasonal variation and ecological niches for azole-resistant environmental A. fumigatus.

Surveillance of ambulance dispatch data as a tool for early warning.

Early detection of disease outbreaks is essential for authorities to initiate and conduct an appropriate response. A need for an outbreak detection that monitored data predating laboratory confirmations was identified, which prompted the establishment of a novel symptom surveillance system. The surveillance system monitors approximately 80% of the Danish population by applying an outbreak detection algorithm to ambulance dispatch data. The system also monitors both regional and national activity and has a built-in, switch-on capacity for implementing symptom surveillance reporting in case of an alert. In an evaluation with outbreak scenarios it was found that decreasing the outbreak detection sensitivity from a prediction limit of 95% to one of 99% moderately reduced the time to detection, but considerably diminished the number of false alerts. The system was able to detect an increased activity of influenza-like illness in December 2003 in a timely fashion. The system has now been implemented in the national disease surveillance programme.

Characteristics of stably expressed human dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor.

Human dopamine D1a and D1b receptors were stably expressed in Baby Hamster Kidney (BHK) or Chinese Hamster Ovary (CHO) cells. [3H]SCH23390 saturation experiments indicated the presence of only a single binding site in the D1a expressing cell line with a Kd of 0.5 nM. In D1b expressing cell lines, two binding sites were observed with Kd values of 0.5 and 5 nM in CHO cells and 0.05 and 1.6 nM in BHK cells, respectively. Neither of the receptors affected Ca2+ metabolism whereas they both were coupled in a stimulatory fashion to adenylyl cyclase. The pharmacological profile of both the D1a and D1b receptors as assessed from inhibition of specific [3H]SCH 23390 binding was classical D1-like. Thus, benzazepine derivatives as well as the atypical neuroleptics, clozapine and fluperlapine, exhibited high affinity whereas D2 selective compounds like sulpiride and spiperone had low affinity for these receptors. Besides SCH 23390, only NNC 112, fluphenazine and bulbocapnine were able to discriminate between the two states of the D1b receptor. In case of the D1a receptor, the Ki values obtained in binding experiments were very similar to Ki values obtained from inhibition of dopamine stimulated adenylyl cyclase. In the D1b expressing cell line, the Ki values obtained from inhibition of the dopamine stimulated adenylyl cyclase indicated a significantly better correlation with the state of the D1b receptor showing high affinity for antagonists. In agreement with observations from binding experiments, dopamine was around 20 fold more potent in stimulating adenylyl cyclase via the D1b receptor as compared to the D1a receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Rheumatoid arthritis of the cricoarytenoid joints: a case of laryngeal obstruction due to acute and chronic joint changes.

A 63-year-old female with severe rheumatoid arthritis and respiratory obstruction with stridor due to cricoarytenoid (c.a.) arthritis is described. Low voltage radiography of the neck revealed erosive changes in the c.a. joints. At laryngoscopy the arytenoids were fixed in adduction, and there were signs of active arthritis. Corticosteroid therapy was instituted with remarkable effect on the obstruction. After the active arthritis had subsided, there remained limited arytenoid mobility with a glottic chink of about 5 mm, but no laryngeal symptoms.

Histomorphometric analysis of iliac trabecular bone in otosclerosis.

With the aim of investigating whether patients with otosclerosis suffer from a generalized bone disorder, a histomorphometric analysis of trabecular bone from the iliac crest was performed. Iliac crest biopsies from 10 patients with otosclerosis and 20 normal controls were obtained after tetracycline double labelling and examined by histomorphometry. No significant differences were found in the estimates of density and remodeling of bone between patients and sex and age-matched normal controls. Qualitatively the bone specimens showed no signs of any generalized bone disorder.

The treatment of perennial rhinitis with a new, non-halogenated, topical, aerosol packed, steroid, Budesonide.

The investigation of a recently synthesized non-halogenated steroid with a high local anti-inflammatory effect and low systemic glucocorticoid effect, on 36 patients with perennial rhinitis was carried out using a double-blind, cross-over technique, where the patients were treated with an aerosol spray containing a concentration corresponding to 200 micrograms/day and 400 micrograms/day of the active compound Budesonide, as well as placebo. There was a significantly better effect from the active compound than from placebo. A dosage-dependent effect was demonstrated for the symptoms nasal blockage and nasal discharge, while this was not so for sneezing bouts. No effect was observed on the function of the suprarenal glands. Local side effects were few and of no importance.

Allergic perennial and non-allergic, vasomotor rhinitis treated with budesonide nasal spray.

A recently synthetized, highly active, non-halogenated steroid, budesonide, in the form of a nasal spray was tested on 21 patients with an allergy demonstrated by means of cutaneous or RAST tests and 15 patients without allergy; these patients were further divided into two groups, 22 with nasal eosinophillia and 14 patients without. There was a significant effect on both patients with vasomotor as well as allergic rhinitis, and in patients with nasal eosinophilia, while this was not the case in the group without eosinophilia. Nasal eosinophilia must be considered an inexpensive and important diagnositic tool for the clarification of perennial rhinitis.

Surgical findings and results of stapedectomy in patients with osteogenesis imperfecta.

Nine patients with osteogenesis imperfecta tarda and stapedial fixation (12 ears) are presented. Surgical findings as well as the immediate and long-term results of stapedectomy are described and compared with the results of previous authors. We found firmly fixed footplates in all 12 ears. Only 2 ears had thick and soft footplates. In 10 ears the stapes crura were abnormally slender and brittle, but only 1 had fractured. In 4 ears a troublesome bleeding tendency occurred during the operation. Both the immediate and the long-term hearing results were in general satisfactory.

Fractures in polyvinyl chloride tracheostomy tubes.

Fracture in polyvinyl chloride tracheostomy tubes in infants and children has not previously been described. On the basis of two events in the same infant a theory for the pathogenesis is outlined, and measures to prevent future cases are described.

Hearing improvement after stapedectomy: up to 19 years' follow-up period.

The long-term results of 925 stapedectomies were analysed after a mean follow-up period of 15 years. Patients who had the operation before the age of 30 were analysed separately. The entire group deteriorated by an average of 0.91 dB/year at 500-2000 Hz, while the under-30 group deteriorated by 0.67 dB/year. There were but slight differences in the conductive component, considering frequencies and age. The perceptive loss/year was not far from that in a normal population.

Histopathology of the stapes in osteogenesis imperfecta.

Conventional histological studies of stapes footplates from patients with osteogenesis imperfecta revealed, in nine out of 15 stapes examined, an otospongiotic-like lesion. Although the morphology of the stapedial lesion was comparable to the early otosclerotic focus, a greater structural disorganization and larger resorption spaces in osteogenesis imperfecta distinguished the two conditions. The histopathology of the stapes was related to the morphology of cortical and trabecular bone from the iliac crest. Various degrees of immature, osteogenic bony tissue were found in the iliac crest, showing no resemblance to the otospongiotic-like focus in the footplate. Even though the histologic appearance of the stapes footplates differed from the findings in peripheral bone, the present study indicates that the stapedial lesion in osteogenesis imperfecta is most likely a manifestation of the generalized bone and connective tissue disorder. The study further supports the view that osteogenesis imperfecta and otosclerosis are of different aetiology.

HLA-A, -B, -C antigens in otosclerosis.

One hundred unrelated, randomly chosen, consecutive patients with otosclerosis, verified by operation, were typed for HLA-A, -B, -C antigens. No significant association between HLA-A, -B, -C antigens and otosclerosis was found.

Bone mineral content in osteogenesis imperfecta tarda and in otosclerosis.

In 22 patients with osteogenesis imperfecta and in 63 patients with otosclerosis the bone mineral content in peripheral bones was determined by photon absorptiometry. The bone mineral content proved significantly reduced in patients with osteogenesis imperfecta as compared with normals and with patients with otosclerosis. In the latter patients the bone mineral content was normal. These findings support the assumption that stapedial fixation in otosclerosis and in osteogenesis imperfecta is of different aetiology.

Limited value of 99mTc depreotide single photon emission CT compared with CT for the evaluation of pulmonary lesions.

OBJECTIVES: A contrast-enhanced multidetector CT (MDCT) scan is the first choice examination when evaluating patients with suspected lung cancer. However, while the clinical focus is on CT, research focus is on molecular biological methods whereby radiolabelled pharmaceuticals are injected into participants and target malignant lung tumours. We examined whether a contrast-enhanced MDCT scan supplied with an additional non-contrast enhanced high-resolution CT scan, or a newer but more expensive (99m)Tc depreotide single photon emission CT (SPECT) scan, was the better first-choice examination for the work-up of pulmonary lesions. Furthermore, we examined whether a (99m)Tc depreotide SPECT scan was an appropriate second-choice examination for patients with indeterminate lesions. METHODS: 140 participants were included in the analysis. CT images were given a malignancy potential rating of 1, 2 or 3 with higher rating being indicative of disease. (99m)Tc depreotide SPECT images were graded either positive or negative. Histopathology and CT follow-up were used as reference standard. Sensitivity, specificity and diagnostic accuracy were calculated. RESULTS: Overall sensitivity, specificity and diagnostic accuracy of CT were 97%, 30% and 84%, respectively. Overall sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 94%, 58% and 76%, respectively. For indeterminate lesions sensitivity, specificity and diagnostic accuracy of (99m)Tc depreotide SPECT were 71%, 68% and 69%, respectively. CONCLUSION: Both CT and (99m)Tc depreotide SPECT made valuable contributions to the evaluation of pulmonary lesions. (99m)Tc depreotide SPECT results were not superior to CT results and did not contribute further to the diagnostic work-up. Regarding indeterminate lesions,( 99m)Tc depreotide SPECT sensitivity was too low.