The genetic heterogeneity of severe von Willebrand disease (vWd) type III was estimated by analysing extended haplotypes of eleven intragenic restriction fragment length polymorphisms and one variable number of tandem repeat polymorphism in 32 patients from 28 families from Germany or of German origin. All patients were screened for gross deletions and for mutations at potential "hot spot" regions of the von Willebrand factor (vWf) gene. Disease-associated haplotypes were established in 24 families. Only a few, apparently unrelated families shared common haplotypes suggesting a considerable genetic heterogeneity in the German population of vWd type III patients. Defects causing vWd type III were identified on 14 out of 56 chromosomes (25%). Gross deletions were detected in two families. A complete homozygous deletion of the vWf gene was displayed in one patient. Another patient was compound heterozygous for a large deletion of at least 100 kb of the vWf gene with an additional, as yet unidentified, defect. One homozygous missense mutation was detected in exon 10, and two nonsense mutations were detected in exon 8 and exon 45 of the vWf gene, respectively. A frameshift mutation (delta C) in exon 18 was identified in five families and an additional frameshift mutation (delta G) was found in exon 28 in one family. It appears that delta C is the most common molecular defect in German patients with vWd type III. Its association with a number of different haplotypes suggests repeated de novo mutations at a mutation "hot spot". Evidence is presented that particular molecular defects causing vWd type III are associated with different patterns of inheritance, depending on their location within the vWf gene. Complete deletions of the gene and nonsense mutations in the pro-sequence are correlated with recessive inheritance, whereas frameshift and nonsense mutations in the gene sequence corresponding to the mature vWf subunit tend to be inherited in a dominant fashion.
Pulmonary compliance and resistance can be reliably corrected even in the presence of a substantial endotracheal tube leak, which makes pulmonary function tests more reliable.
Due to the short airways in premature children, an accurate position of the endotracheal tube (ETT) is crucial for adequate mechanical ventilation. Verification of ETT-position is done in chest radiographs. However, ETT-position varies substantially with head movement. When the head is flexed, the tube might appear too deeply inserted, and inadvertent extubation may occur in cases of retraction of ETT after radiography. Extension of the cervical spine will suggest an inappropriately high ETT-position, so that intended corrections can lead to main-stem intubation. Radiographic visible skeletal structures could serve as reference points to allow the detection of head declination and imperfect positioning of ETT. Ratios of anatomical landmarks were used to estimate head position. In this study, 111 radiographs of 24 preterm neonates with a gestational age of 24-29 weeks and weights of 500-1,000 g were analyzed. A mathematical algorithm for the detection and correction of ETT-positions, based on common chest radiographs, was developed. In 108 cases (97.3%), ETT-distance from the midtracheal level was less than 2 mm after use of the proposed correction.Thus, the suggested correction equation for head position enables verification of the actual ETT-position without requiring a defined placement of the head during radiography. Moreover, it can be helpful for estimating the depth of ETT-insertion in conditions when radiography is not available.
Measurements of lung compliance (C) and resistance (R) are influenced by endotracheal tube leaks (ETTL) as well as non-linear pressure/volume relationships (P/V relationship). To keep C and R reliable, we developed an algorithm to mathematically correct inspiratory and expiratory volume (V) and flow. In this study, a ventilated lung model for non-linear P/V relationship with adjustment of an increasing ETTL was studied. In addition, the recordings (airway pressure, flow, and volume) of 21 infants (median weight: 1,220 g, range: 640-2,160 g, with a median leak size of 32%, range: 24-56%) were investigated. C and R were calculated continuously from the recordings of flow, volume, and airway pressure over time according to the changing volume. A method especially developed for the analysis of non-linear pressure-volume-relationship (APVNL) was employed. C and R affected by leaks were corrected applying the newly developed mathematical algorithm and compared with measurements without leakage. C could be corrected up to a leak of 80% and R up to 55% leak at half tidal V for the model with non-linear P/V-R. C and R without leak and after leak correction did not differ significantly in all infants where the APVNL method was applied (P > 0.05).
The accuracy of the calculation of intratracheal pressure ensures adequate monitoring of artificial ventilation, even in the presence of endotracheal tube leaks. This might decrease the risk of barotrauma and improve the effectiveness of ventilation.
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