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PubMed2002

Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A.

The messenger RNA (mRNA) from 5 of 69 patients with severe hemophilia A did not support amplification of complementary DNA containing the first few exons of the factor VIII (F8) gene but supported amplification of mRNA containing exon 1 of F8 plus exons of the VBP1 gene. This chimeric mRNA signals an inversion breaking intron 1 of the F8 gene. Using an inversion patient, one deleted for F8 exons 1 to 6, and cosmids mapped 70 to 100 kb telomeric of the F8 gene, this study shows that this break strictly affects a sequence (int1h-1) repeated (int1h-2) about 140 kb more telomerically, between the C6.1A and VBP1 genes. The 1041-base pair repeats differ at a single nucleotide (although int1h-2 also showed one polymorphism) and are in opposite orientation. The results demonstrate that they cause inversions by intrachromosome or intrachromatid homologous recombination. The genomic structure of the inversion region shows that transcription traverses intergenic spaces to produce the 2 chimeric mRNAs containing the F8 sequences and characteristic of the inversion. This observation prompts the suggestion that nature may use such extended transcription to test whether the addition of novel domains from neighboring genes creates desirable new genes. A rapid polymerase chain reaction test was developed for the inversion in both patients and carriers. This has identified 10 inversions, affecting F8 genes with 5 different haplotypes for the BclI, introns 13 and 22 VNTR polymorphism, among 209 unrelated families with severe hemophilia A. This indicates a prevalence of 4.8% and frequent recurrence of the inversion. This should result in absence of F8, and one inversion patient is known to have inhibitors. (Blood. 2002;99:168-174)

Base Sequence↗

PubMed2001

[Pericentric inversion of human chromosomes and its risks] ].

Pericentric inversions of human chromosomes represent rearrangements are formed between two breaks on the short and on long arms of the chromosome with following rotation and new connection of the separated segment in the reversed position. The abnormality does not result in most of the carriers to any clinical manifestations. However, the basic risk the carriers of such inversion are exposed is the possibility of formation of a recombinant aneusomy--later transformation of the inverted chromosome during gametogenesis. Conception by the recombinant gamete usually results in spontaneous abortion or to a birth of seriously affected individual. The risk of recombination has to be in every newly registered inversion individually considered. The larger part of chromosome is taken into the pericentic inversion, the smaller is the extent of resulting duplication and smaller is the deficiency of chromosomal parts, which results from the recombination. The higher is then the viability of the affected foetus. In families with detected recombination, chromosomal examination is fully recommended. Prenatal examination is also indicated when the transformation is listed among the risk inversions or it has larger extent then recorded inversions. Beside the risk inversions, also the "safe" inversions exist, which include minor and frequently occurring transformation of chromosome No 2--inv(2)(p11q13) and inversion of chromosome 10--inv(10)(p11q21).

Chromosome Aberrations↗

PubMed2003

[Long distance-PCR for detection of factor VIII gene inversion in patients with severe hemophilia A].

The aim of current study was to detect intron 22 inversion of factor VIII gene in severe hemophilia A (HA) patients and screen the carriers of the gene inversion. Fifty-five cases of severe HA were involved and factor VIII gene inversion was detected and identified by long distance-PCR (LD-PCR) and 0.6% agarose gel electrophoresis. The 11 kb and 12 kb bands indicate the factor VIII gene inversion and non-inversion, respectively. Occurring of both 11 kb and 12 kb bands indicates a carrier of the inversion. The results showed that factor VIII gene inversion existed in 22 out of 55 cases, which accounted for about 40% of total detected patients. Five carriers of factor VIII gene inversion were diagnosed from the members in 15 families. In conclusion, LD-PCR assay is a simple, rapid and accurate method for detection of factor VIII gene inversion, and this approach is helpful in screening, carrier testing, and prenatal diagnosis of severe hemophilia A.

Adolescent↗

PubMed1994

[Variability of inversion polymorphism in populations of Drosophila lummei, Hackman].

Comparison of inversion polymorphism in Drosophila lummei populations from Finland (Kemi) and Russia (Rybnyi) revealed additional species-specific paracentric inversions in chromosomes 2-4. The newly found inversions, 2V, 3M, 4U, and V, were reported only for the Russian population. The 2U inversion had been earlier detected in D. lummei and in the second chromosome of a D. ezoana population from Kamchatka. Species-specific 5T inversion from the Finland population was not found in the Russian population. 4R, S, and 5S inversions were common for both populations but had different sample frequencies. 4R and 5S inversions were more frequent in the Finland, and 4S in the Russian population which may indicate their different adaptive values in these areas. All inversions except 3M were localized in subterminal chromosome regions. 3M inversion was localized in the submedian region.

Animals↗

PubMed1998

Population genetics of inversion polymorphism in Drosophila ananassae.

Drosophila ananassae, although a cosmopolitan and domestic species, is largely circumtropical in distribution. It occupies unique status in the whole of genus Drosophila due to certain peculiarities in its genetical behaviour. The most unusual feature of this species is spontaneous male recombination in appreciable frequency. This species is of common occurrence in India. Population genetics of inversion polymorphism has been extensively studied in Indian D. ananassae in our laboratory. The main findings are: (i) Three cosmopolitan inversions namely AL in 2L, DE in 3L and ET in 3R are of frequent occurrence in Indian populations and have become coextensive with the species. (ii) Quantitative data on the frequency of three cosmopolitan inversions in 29 natural populations of D. ananassae suggest that there is a considerable degree of genetic divergence at the level of inversion polymorphism. In general, the populations from south India show more differentiation than those from the north. (iii) These three cosmopolitan inversions exhibit heterosis. Interracial hybridization does not lead to breakdown of heterosis, which suggests that evidence for coadaptation is lacking in geographic populations of D. ananassae. Heterosis appears to be simple luxuriance rather than populational heterosis (coadaptation). (iv) Data on intra- and interchromosomal associations in natural and laboratory populations of D. ananassae show that interchromosomal associations occur randomly indicating no interchromosomal interactions but two inversions of the third chromosome often show strong linkage disequilibria in laboratory populations which is due to epistatic interaction and suppression of crossing over. The role of genetic drift causing linkage disequilibria in isofemale strains of D. ananassae has also been suggested. (v) Mating ability of homo- and hetero-karyotypes due to subterminal (2L) inversion derived from natural populations of D. ananassae in which the frequency of different chromosome arrangements were known, was tested and the results indicate that the chromosome occurring in high frequency is associated with higher mating activity in all the populations analysed and heterokaryotypic males are superior in mating propensity to the corresponding homokaryotypes, indicating the existence of heterosis associated with the AL inversion with respect to male mating activity. Thus inversion polymorphism in D. ananassae may have a partial behavioural basis as has been demonstrated in other species of Drosophila.

Animals↗

PubMed2002

Inverse 15N-metabolic labeling/mass spectrometry for comparative proteomics and rapid identification of protein markers/targets.

The inverse labeling/mass spectrometry strategy has been applied to protein metabolic (15)N labeling for gel-free proteomics to achieve the rapid identification of protein markers/targets. Inverse labeling involves culturing both the perturbed (by disease or by a drug treatment) and control samples each in two separate pools of normal and (15)N-enriched culture media such that four pools are produced as opposed to two in a conventional labeling approach. The inverse labeling is then achieved by combining the normal (14)N-control with the (15)N-perturbed sample, and the (15)N-control with the (14)N-perturbed sample. Both mixtures are then proteolyzed and analyzed by mass spectrometry (coupled with on-line or off-line separation). Inverse labeling overcomes difficulties associated with protein metabolic labeling with regard to isotopic peak correlation and data interpretation in the single-experiment approach (due to the non-predictable/variable mass difference). When two data sets from inverse labeling are compared, proteins of differential expression are readily recognized by a characteristic inverse labeling pattern or apparent qualitative mass shifts between the two inverse labeling analyses. MS/MS fragmentation data provide further confirmation and are subsequently used to search protein databases for protein identification. The methodology has been applied successfully to two model systems in this study. Utilizing the inverse labeling strategy, one can use any mass spectrometer of standard unit resolution, and acquire only the minimum, essential data to achieve the rapid and unambiguous identification of differentially expressed protein markers/targets. The strategy permits quick focus on the signals of differentially expressed proteins. It eliminates the detection ambiguities caused by the dynamic range of detection. Finally, inverse labeling enables the detection of covalent changes of proteins responding to a perturbation that one might fail to distinguish with a conventional labeling experiment.

Amino Acid Sequence↗

PubMed2004

Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.

RATIONALE: In order to determine the possible relationship between antipsychotic drug properties and inverse agonist activity at h5HT6 and h5HT7 receptors, constitutively activated forms of these receptors were created by site-specific mutagenesis. Typical and atypical antipsychotic drugs were assayed for their potencies as inverse agonists at these mutated receptors. OBJECTIVES: Stable cell lines expressing constitutively activated forms of the h5HT6 and h5HT7 receptors were created. Typical and atypical antipsychotic drugs demonstrating high to moderate affinities for the h5HT6 and h5HT7 receptors were assayed for their potencies in reversing the agonist-independent activity (inverse agonist activity). RESULTS: The E322R h5HT6 mutant and the S267K h5HT7 mutant displayed sufficiently robust agonist-independent activity when expressed in stable cell lines to allow the detailed, concentration-dependent, investigation of the inverse agonist activity of typical and atypical antipsychotic drugs. All the drugs tested displayed inverse agonist activity at both the activated h5HT6 and h5HT7 receptors. Native forms of these receptors did not display any constitutive activity. Interestingly, atypical antipsychotic drugs displayed potent inverse agonist activity, relative to typical antipsychotic drugs, at the h5HT7 receptor. LSD displayed neutral antagonist properties at the mutant h5HT7 receptor. CONCLUSIONS: Site-specific mutations in the third intracellular loop of the G(s)-coupled h5HT6 and h5HT7 receptors produce constitutive activation. Antipsychotic drugs display inverse agonist activity at the activated receptors. The inverse agonist mechanism-of-action of the atypical antipsychotic drugs at the h5HT7 receptors may be different from the typical antipsychotic drugs as these drugs displayed far higher potencies as inverse agonists at the h5HT7 receptor.

Amino Acid Substitution↗

PubMed2005

Cortical correlates of face and scene inversion: a comparison.

Face recognition is more strongly impaired by stimulus inversion than nonface object recognition. This phenomenon, known as the face inversion effect (FIE), suggests that the visual system contains specialized processing mechanisms that are more engaged by upright faces than by inverted faces or nonface objects. Neuroimaging and neuropsychological studies indicate that environmental scenes may also recruit specialized-purpose processing machinery but a comparable inversion effect for scenes has not been established. Here we demonstrate that both face and scene inversion lead to behavioral penalties during performance of a continuous visual matching task; however, the scene inversion effect was less robust and declined in magnitude over the course of the experiment. Scene inversion led to greater neural response in the functionally defined lateral occipital (LO) object area for inverted versus upright scenes and reduced response in the parahippocampal place area (PPA), while face inversion lead to greater response in LO and the right middle fusiform (MF) object area for inverted versus upright faces but no change in the fusiform face area (FFA). A whole-brain analysis revealed several regions that responded more strongly to either upright versus inverted faces or upright versus inverted scenes, some of which may be involved in post-recognition processing. These results demonstrate that both face and scene inversion cause a shift from specialized processing streams towards generic object-processing mechanisms; however, this shift only leads to a reliable behavioral penalty in the case of face inversion.

Adolescent↗

PubMed2003

A comparison of forward and inverse treatment planning for intensity-modulated radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. RESULTS: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. CONCLUSION: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance.

Head and Neck Neoplasms↗

PubMed2006

Molecular basis of melanocortin-4 receptor for AGRP inverse agonism.

We have investigated receptor structural components of the melanocortin-4 receptor (MC4R) responsible for ligand-dependent inverse agonism. We utilized agouti-related protein (AGRP), an inverse agonist which reduces MC4R basal cAMP production, as a tool to determine the molecular mechanism. We tested a series of chimeric receptors and utilized MC4R and MC1R as templates, in which AGRP is an inverse agonist for MC4R but not for MC1R. Our results indicate that replacements of the extracellular loops 1, 2 and 3 of MC4R with the corresponding regions of MC1R did not affect AGRP inverse agonist activity. However, replacement of the N terminus of MC4R with the same region of MC1R decreases AGRP inverse agonism. Replacement of transmembrane domains 3, 4, 5 and 6 of MC4R with the corresponding regions of MC1R did not affect AGRP inverse agonist activity but mutation of D90A in transmembrane 2 (TM2) and D298A in TM7 abolished AGRP inverse activity. Deletion of the distal MC4R C terminus fails to maintain AGRP mediated reduction in basal cAMP production although it maintains NDP-MSH mediated cAMP production. In conclusion, our results indicate that the N terminus and the distal C terminus of MC4R do appear to play important roles in AGRP inverse agonism but not NDP-MSH mediated receptor activation. Our results also indicate that the residues D90 in TM2 and D298 in TM7 of hMC4R are involved in not only NDP-MSH mediated receptor activation but also AGRP mediated inverse agonism.

Agouti-Related Protein↗

PubMed1997

Mechanistic studies on metabolic chiral inversion of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of the new anti-rheumatic agent 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), in rats.

The chiral inversion properties of 4-(4-methylphenyl)-2-methylthiomethyl-4-oxobutanoic acid (KE-748), an active metabolite of 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298), were compared with those of ibuprofen in rats. After administration of R(-)-[2 alpha-2H]KE-748, S(+)-KE-748 was present in the rat plasma, and the deuterium atoms of the S(+)-enantiomer were almost all replaced by hydrogen atoms. After administration of S(+)-[2 alpha-2H]KE-748, the deuterium content of S(+)-KE-748 in the plasma remained intact. In the in vitro study, using a cell-free system and rat liver homogenates, the chiral inversion of ibuprofen was apparent when both CoA and ATP were present; however, KE-748 was not inverted. In the study on isolated rat hepatocytes, the unidirectional chiral inversion from R(-)-to S(+)-enantiomer was observed for both ibuprofen and KE-748. When R(-)-ibuprofen was incubated with medium and long chain fatty acids (carbon chain length C6 to C16), using isolated hepatocytes, the chiral inversion decreased significantly. On the other hand, when R(-)-KE-748 was incubated with short and medium chain fatty acids (carbon chain length C3 to C8), chiral inversion was inhibited markedly. To induce hepatic microsomal long chain fatty acid CoA ligase, rats were treated with clofibric acid (CF rats). In both in vitro and in vivo experiments on CF rats, chiral inversion from R(-)-to S(+)-ibuprofen was enhanced significantly compared with that in controls, whereas the enhancement was not observed in the case of R(-)-KE-748. There was no influence of benzoic acid, a typical substrate on medium chain fatty acid CoA ligase in the mitochondrial matrix, on chiral inversion of R(-)-ibuprofen, using, isolated hepatocytes. In contrast, the chiral inversion from R(-)-to S(+)-KE-748 was strongly inhibited in the presence of benzoic acid. These results indicate that chiral inversion of R(-)-KE-748 may proceed via formation of the CoA-thioester intermediate with loss of the 2 alpha-methine proton, in a manner similar to that seem with R(-)-ibuprofen. However, the enzymes needed to form CoA-thioester of R(-)-KE-748 differ from those for R(-)-ibuprofen.

Animals↗

PubMed1990

Physiological interpretations based on lumped element models fit to respiratory impedance data: use of forward-inverse modeling.

Respiratory impedance (Zrs) data at lower (less than 4 Hz) and higher (greater than 32 Hz) frequencies require more complicated inverse models than the standard series combination of a respiratory resistance, inertance, and compliance. In this paper, a forward-inverse modeling approach was used to provide insight on how the parameters in these more complicated inverse models reflect the true physiological system. Forward models are set up to incorporate explicit physiological and anatomical detail. Simulated forward data are then fit with identifiable inverse models and the parameter estimates related to the known detail in the forward model. It is shown that inverse fitting of low frequency data alone will not allow a distinction between frequency dependence due to airway inhomogeneities and frequency dependence due to tissue viscoelasticity. With higher frequency data, a forward model based on an asymmetric branching airways network was used to simulate Zrs from 0.1-128 Hz with increasing amounts of nonuniform peripheral airway obstruction. Here, inverse modeling is more amenable to sensibly separating estimates of airway and tissue properties. A key result, however, is that changes in the tissue parameters of an inverse model (which provides an excellent fit to Zrs data) will appropriately occur in response to inhomogeneous alterations in airway diameters only. The apparent altered tissue properties reflect the decreased communication of some tissue segments with the airway opening and not an explicit change at the tissue level. These phenomena present a substantial problem for the inverse modeler. Finally, inverse model fitting of low and high frequency Zrs data simultaneously with a single model is not helpful for extracting additional physiological detail. Instead, separate models should be applied to each frequency range.

Airway Obstruction↗

PubMed1984

Evidence for heterosynaptic pairing of the inverted segment in pericentric inversion heterozygotes of the deer mouse (Peromyscus maniculatus).

Silver-stained pachytene cells of male deer mice, Peromyscus maniculatus, which were heterozygous for a naturally occurring pericentric inversion of chromosome 6, were analyzed by light microscopy. The presence of the terminally positioned inversion, involving approximately 30% of the length of chromosome 6, was detected by G-banding. Within the inversion, C-band-positive heterochromatin was restricted to the centromeric region. Silver-staining of spermatocytes revealed the synaptonemal complexes (SCs) of the autosomal bivalents and the X-Y chromosome association. Pachytene cells were scored for the presence of inversion loops corresponding to the pericentric inversion of chromosome 6. Possible loop 6 configurations were detected in less than 1% of the cells examined, the vast majority of cells having regularly formed autosomal SCs similar to those reported for homomorphic chromosome pairs in other rodent species. It appears, therefore, that in these mice the inverted region of chromosome 6 was heterosynaptic throughout pachytene. Heterosynapsis is hypothesized as a mechanism which might obviate the production of duplication and deletion chromatids expected from crossing-over in pericentric inversion loops. The observation of heterosynaptic pairing in the inverted segment and the hypothesis of inversion heterosynapsis as a mechanism averting gametic loss are consistent with the widespread occurrence of pericentric inversion polymorphisms in P maniculatus and the apparent failure of pericentric inversions to genetically isolate populations of this species.

Animals↗

PubMed2000

Transient U wave inversion during treadmill exercise testing in patients with left anterior descending coronary artery disease.

The transient U wave inversion during exercise is specific for detecting left anterior descending coronary artery (LAD) disease. In a homogeneous patient group restricted to LAD disease, however, the significance of the electrocardiographic finding has not yet been clarified. Thus, clinical characteristics in patients with angiographically documented one-vessel disease of the LAD and exercise-induced U wave inversion were delineated. Symptom-limited treadmill exercise testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years) with angina pectoris whose culprit lesion was located only in the LAD. U wave polarity and amplitude were determined before, during, and after exercise with the P-Q segment as the isoelectric line. Exercise-induced transient U wave inversion was defined as positive when there was a discrete negative deflection > or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise-induced U wave inversion. There were no differences in age, male gender, antianginal medication use, and coronary angiographic data between the two patients groups: patients with and without U wave inversion. Heart rate and double product of heart rate and systemic systolic blood pressure at peak exercise were also similar. Prevalence of abnormal exercise-induced S-T segment shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with and without U wave inversion, respectively. The difference was statistically significant (p = 0.02). Among patients with exercise-induced S-T segment shift, the proportion of patients with S-T segment elevation to all the patients was larger in patients with U wave inversion than in patients without U wave inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In conclusion, the exercise-induced U wave inversion in patients with one-vessel disease of the LAD indicates the severe degree of myocardial ischemia induced in the territory perfused by the LAD. However, the electrocardiographic finding does not appear to have independent significance since it closely correlates with the presence of S-T segment shift.

Aged↗

PubMed2004

Inverse planning in three-dimensional conformal and intensity-modulated radiotherapy of mid-thoracic oesophageal cancer.

The aim of this study is to demonstrate the use of inverse planning in three-dimensional conformal radiation therapy (3DCRT) of oesophageal cancer patients and to evaluate its dosimetric results by comparing them with forward planning of 3DCRT and inverse planning of intensity-modulated radiotherapy (IMRT). For each of the 15 oesophageal cancer patients in this study, the forward 3DCRT, inverse 3DCRT and inverse IMRT plans were produced using the FOCUS treatment planning system. The dosimetric results and the planner's time associated with each of the treatment plans were recorded for comparison. The inverse 3DCRT plans showed similar dosimetric results to the forward plans in the planning target volume (PTV) and organs at risk (OARs). However, they were inferior to that of the IMRT plans in terms of tumour control probability and target dose conformity. Furthermore, the inverse 3DCRT plans were less effective in reducing the percentage lung volume receiving a dose below 25 Gy when compared with the IMRT plans. The inverse 3DCRT plans delivered a similar heart dose as in the forward plans, but higher dose than the IMRT plans. The inverse 3DCRT plans significantly reduced the operator's time by 2.5 fold relative to the forward plans. In conclusion, inverse planning for 3DCRT is a reasonable alternative to the forward planning for oesophageal cancer patients with reduction of the operator's time. However, IMRT has the better potential to allow further dose escalation and improvement of tumour control.

Esophageal Neoplasms↗

PubMed1998

The physiologic effects of inverse ratio ventilation.

STUDY OBJECTIVES: The efficacy of inverse ratio ventilation in ARDS is not clear. Furthermore, the mechanism responsible has not been determined. We designed an animal study to determine if inverse ratio ventilation improves gas exchange and by what mechanism. DESIGN: Prospective randomized, controlled design was used. SETTING: University of Missouri Pulmonary/Critical Care Animal Laboratory. PARTICIPANTS: Nine dogs with oleic acid-induced lung injury as control animals to assess stability of the model, nine in the experimental model. INTERVENTIONS: Conventional ventilation with full recruitment extrinsic positive end-expiratory pressure (PEEP) was compared with two other modes of ventilation. One was inverse ratio with extrinsic PEEP and the second was inverse ratio with intrinsic PEEP equal to full recruitment PEEP. Full recruitment levels of PEEP were defined by optimizing compliance, then increasing PEEP by 2.5 cm/H2O. Each type of ventilation was maintained for 45 min after the edema had stabilized. Comparison of lung injury over time requires stability of the model over time. Therefore, we also assessed the stability of the preparation over time by examining compliance, extravascular lung water, and venous admixture in nine control dogs with equivalent lung injury over the same time span. MEASUREMENTS AND RESULTS: Mean airway pressure was increased by both types of inverse ratio ventilation, while compliance remained stable. Venous admixture was reduced (conv=0.32+/-0.12, inverse ratio with extrinsic PEEP=0.24+/-0.10, inverse ratio with intrinsic PEEP=0.28+/-0.11) with inverse ratio with extrinsic PEEP, but the improvement was less with inverse ratio with intrinsic PEEP, even though the mean airway pressure was higher. CONCLUSIONS: We conclude that increasing mean airway pressure by prolongation of the inspiratory time improves gas exchange in our model of ARDS, but when mean airway pressure is increased further, allowing the development of intrinsic PEEP, the beneficial effects on gas exchange are less. Increasing mean airway pressure with intrinsic PEEP is not equivalent to other methods of increasing mean airway pressure.

Airway Resistance↗

PubMed2001

Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases.

OBJECTIVE: The purpose of our study was to assess whether phase-inversion sonography during the late, liver-specific phase of contrast enhancement using Levovist improves the detection of hepatic metastases relative to unenhanced conventional B-mode sonography. SUBJECTS AND METHODS: Sixty-two patients were studied with unenhanced B-mode sonography and phase-inversion sonography 2.5 min after the injection of Levovist. All patients underwent one reference examination (CT, MR imaging, or intraoperative sonography). The conspicuity, number, size, and distribution of metastases before and after contrast administration as judged by a sonographer (who was unaware of other imaging findings) were compared with each other and with reference imaging. RESULTS: The conspicuity of metastases was improved by contrast-enhanced phase inversion in 94% of patients. Thirty-nine patients showed metastases on reference imaging; 36 of these were positive on baseline sonography and 38 on phase-inversion sonography. Phase-inversion sonography showed more reference imaging-confirmed metastases than baseline sonography in 28 patients (45%). The average number of confirmed metastases per patient was 3.06 for baseline sonography and 5.42 for contrast-enhanced phase-inversion sonography (p < 0.01). The average sensitivity for detecting individual metastases improved from 63% to 91%. Metastases of less than 1 cm were shown in 14 patients on baseline sonography, in 24 patients on phase-inversion sonography, and in 26 on reference imaging. Both sonographic techniques showed false-positive lesions in six patients. CONCLUSION: Contrast-enhanced phase-inversion sonography in the liver-specific phase of contrast enhancement using Levovist provides a marked improvement in the detection of hepatic metastases relative to unenhanced conventional sonography, without loss of specificity. Phase-inversion sonography was particularly advantageous in detecting small metastases and may be a competitive alternative to CT and MR imaging.

Adult↗

PubMed2001

Mechanical percussion, inversion and diuresis for residual lower pole fragments after shock wave lithotripsy: a prospective, single blind, randomized controlled trial.

PURPOSE: We compare the effectiveness of mechanical percussion and inversion with observation for eliminating lower caliceal fragments 3 months after shock wave lithotripsy. MATERIALS AND METHODS: At 3 months after shock wave lithotripsy 69 patients with residual lower caliceal fragments 4 mm. or less were randomized to receive either mechanical percussion and inversion or observation for 1 month. The observation group then received crossover mechanical percussion and inversion if fragments persisted. All patients were followed with plain film of the kidneys, ureters and bladder to assess the stone area and stone-free status, and renal tomography or noncontrast spiral computerized tomography to confirm stone-free status. A blinded radiologist reviewed all films. Patients were treated with a mechanical chest percussor applied to the flank while inverted to greater than 60 degrees after receiving 20 mg. furosemide. RESULTS: A total of 35 patients were randomized to receive immediate mechanical percussion and inversion therapy and 34 observation. Of the patients in the observation group 28 subsequently received mechanical percussion and inversion after completing the observation period. The groups were not different in gender, body mass index, side affected, stone location or renal anatomical features. The mechanical percussion and inversion group had a substantially higher stone-free rate than the observation group (40% versus 3%, respectively, p <0.001). The mechanical percussion and inversion group also had a greater improvement in total stone area than controls (-63.3% versus +2.7%, respectively, p <0.001). No significant adverse effects were noted in the mechanical percussion and inversion group. CONCLUSIONS: Mechanical percussion and inversion is a safe and effective treatment option for residual lower caliceal fragments 3 months after shock wave lithotripsy. Nearly 50% of patients become stone-free, and stone burden is decreased by 50% in the remainder.

Adult↗