A patient with myelofibrosis complicated by refractory ascites and portal hypertension: to tips or not to tips? A case report with discussion of the mechanism of ascites formation

In patients with myelofibrosis, clinically significant portal hypertension is known to be predominantly presinusoidal; however, the exact mechanisms are still controversial. The pathophysiology is particularly enigmatic in those patients without histological and angiographic evidence of significant intra- or extrahepatic obstruction to portal blood flow, respectively. Moreover, ascites formation has been reported in such cases, but in general is rare in presinusoidal portal hypertension. Here we present such a patient in which ascites developed even in the presence of unchanged serum protein levels (oncotic pressure) and was refractory to sodium restricted diet and high-dose diuretic treatment. A discussion on the parameters influencing fluid exchange and ascites formation particularly emphasizing the potential importance of the hyperdynamic circulation in this case is given. Finally, the patient was treated by implanting a transjugular intrahepatic shunt (TIPS), exerting a diuretic effect sufficient enough to avoid re-formation of ascites for several months. However, ascites re-accumulated potentially due to the appearance of ectopic peritoneal myeloid metaplasia and the patient died soon afterwards. In conclusion, TIPS may be considered as rescue management for refractory ascites secondary to portal hypertension, but caution in respect to the presence and/or development of peritoneal or other ectopic haematopoesis has to be taken.     

Extensor mechanism slide for the treatment of proximal interphalangeal joint extension lag: an anatomic study

PURPOSE: We describe a technique for correction of proximal interphalangeal joint (PIP) extensor lag secondary to angulation and/or shortening of proximal phalanx fractures. METHODS: Proximal phalanx fracture malunions with 2.5 mm of shortening, 5.0 mm of shortening, and apex volar angulation of 40 degrees were simulated in 15 cadaver fingers, creating PIP extensor lags. The metacarpophalangeal (MCP) joint was pinned in neutral. Transection of the ulnar and radial sagittal bands, the extensor digitorum communis (EDC) insertion on the MCP joint capsule, and the juncturae tendinae then was performed. The PIP extensor lag before and after each of the earlier-noted releases was recorded. The MCP joint then was freed and MCP hyperextension was recorded. With the MCP joint in neutral position the sagittal bands then were reapproximated with sutures and MCP extension was measured. RESULTS: The 2.5 mm of axial shortening, 5.0 mm of axial shortening, and 40 degrees of apex volar angulation fracture models produced an average extensor lag of 6.2 degrees , 25.8 degrees , and 42.5 degrees , respectively. Maximal correction of PIP extensor lag required transection of both sagittal bands, EDC insertion on the MCP capsule, and the juncturae tendinae with an average residual extensor lag of -0.8 degrees for the 2.5-mm shortening model, 0.7 degrees for the 5.0-mm shortening model, and 3.2 degrees for the 40 degrees -angulation model. The MCP joint hyperextension increased by 20 degrees to 30 degrees after the releases but decreased to only 1.8 degrees if the sagittal bands were reapproximated to the EDC tendon at their new resting position with the MCP joint in neutral position. CONCLUSIONS: In the cadaver model the PIP extensor lag can be improved substantially by transection of the sagittal bands, release of the EDC insertion on the MCP capsule, transection of the juncturae tendinae, and reapproximation of the sagittal bands to the EDC tendon.     

Affected-sib-pair test for linkage based on constraints for identical-by-descent distributions corresponding to disease models with imprinting

Holmans' possible triangle test for affected sib pairs has proven to be a powerful tool for linkage analysis. This test is a likelihood-ratio test for which maximization is restricted to the set of possible sharing probabilities. Here, we extend the possible triangle test to take into account genomic imprinting, which is also known as parent-of-origin effect. While the classical test without imprinting looks at whether affected sib pairs share 0, 1, or 2 alleles identical-by-descent, the likelihood-ratio test allowing for imprinting further distinguishes whether the sharing of exactly one allele is through the father or mother. Thus, if the disease gene is indeed subject to imprinting, the extended test presented here can take into account that affecteds will have inherited the mutant allele preferentially from one particular parent. We calculate the sharing probabilities at a marker locus linked to a disease susceptibility locus. Using our formulation, the constraints on these probabilities given by Dudoit and Speed ([1999] Statistics in Genetics; New York: Springer) can easily be verified. Next, we derive the asymptotic distribution of the restricted likelihood-ratio test statistic under the null hypothesis of no linkage, and give LOD-score criteria for various test sizes. We show, for various disease models, that the test allowing for imprinting has significantly higher power to detect linkage if imprinting is indeed present, at the cost of only a small reduction in power in case of no imprinting. Altogether, unlike many methods currently available, our novel model-free sib-pair test adequately models the epigenetic parent-of-origin effect, and will hopefully prove to be a useful tool for the genetic mapping of complex traits.     

A randomized controlled trial on the effect of montelukast on sputum eosinophil cationic protein in children with corticosteroid-dependent asthma

Previous adult studies demonstrated the clinical efficacy of an additional treatment with leukotriene receptor antagonists on steroid-dependent asthma, but there is little knowledge about anti-inflammatory add-on effects within the lung. In this study, we hypothesized that steroid-treated children exhibit a decrease in bronchial inflammation in induced sputum under additional treatment with montelukast. Twenty-five asthmatic children aged 6 to 14 y, who had been taking inhaled corticosteroids (400-800 microg/d budesonide) regularly for at least 12 wk, were randomized to receive additional treatment with either montelukast (5 mg orally, once daily) or placebo over a 4-wk period. As primary efficacy variable, eosinophil cationic protein (ECP) in induced sputum as direct measurement of bronchial inflammation was assessed before and after treatment. To assure a baseline level of inflammation, an ECP concentration above 100 microg/L was required. Sputum eosinophil count, concentration of exhaled nitric oxide, urinary excretion of eosinophil protein X, and quality-of-life items were considered as secondary outcome variables. After treatment with montelukast, ECP in sputum was significantly reduced (montelukast: median -975 microg/L [5 to 95% confidence interval: -4295 to 583 microg/L]; placebo: 561 microg/L [-1335 to 3320 microg/L]; p < 0.01) and the quality-of-life score had significantly improved (p < 0.05) compared with placebo. Partly explained by low baseline levels, no statistically significant change in concentration of exhaled nitric oxide (p > 0.05), urinary excretion of eosinophil protein X (p > 0.05), or eosinophil count (p > 0.05) was found. In conclusion, add-on treatment with montelukast can suppress sputum ECP in children with steroid-dependent asthma, while at the same time an improvement in quality of life items occurs.     

NF-kappaB regulates intestinal epithelial cell and bile salt-induced migration after injury

OBJECTIVE: To determine if NF-kappa B regulates intestinal epithelial cell migration and if it has a role during bile salt-induced migration. SUMMARY BACKGROUND DATA: Mucosal restitution is an important repair modality in the gastrointestinal tract. The authors have shown that taurodeoxycholate (TDCA) increases intestinal epithelial cell migration. NF-kappa B regulates activation of a number of genes involved in inflammatory responses. METHODS: Studies were conducted in IEC-6 cells. I kappa B protein expression was determined by Western blot analysis. Sequence-specific NF-kappa B binding activity was measured by EMSA shift assays and nuclear localization by immunohistochemistry. Cell migration was examined by using an in vitro model that mimics the early cell division-independent stages of epithelial restitution. RESULTS: The process of cell migration over the wounded area was associated with a significant increase in NF-kappa B binding activity in IEC-6 cells. Immunohistochemistry revealed translocation of NF-kappa B into the nucleus. Western blot analysis showed that injury decreased I kappa B protein expression. Inhibition of the binding activity by treatment with a specific NF-kappa B inhibitor, MG-132, inhibited cell migration during restitution. Further, exposure to TDCA at the physiologic concentration that induces intestinal epithelial cell migration increased NF-kappa B binding activity, induced NF-kappa B translocation into the nucleus, and decreased I kappa B protein expression. MG-132 also inhibits bile salt-induced cell migration. CONCLUSIONS: NF-kappa B regulates intestinal epithelial cell migration. Bile salts at physiologic concentrations increase cell migration by activation of NF-kappa B. These data show that bile salts may have a role in the maintenance of intestinal mucosal integrity.     

Hautkrankheiten

Ohne Zusammenfassung     

Replacement of upper esophagus: Results with myocutaneous flap and with gastric transposition

The authors reviewed 25 cases of pharyngoesophageal replacement. A tubed pectoralis major myocutaneous flap was employed in ten cases where an adequate distal resection margin could be obtained above the thoracic inlet. Total gastric transposition was used in 15 cases where resection extended into the mediastinum. The overall rates of complications (52%), postoperative mortality (20%), and satisfactory deglutition (80%) were similar for both operations and were superior to those achieved with reconstructive procedures previously used by the authors. The choice of method is influenced by the length of the pharyngoesophagus to be replaced and the general condition of the patient. Gastric transposition is a more versatile operation and is adaptable to replacement of the entire esophagus if necessary, while the tubed pectoralis major myocutaneous flap has proven particularly effective for the rehabilitation of elderly and severely debilitated patients.