Quality of life in patients with various liver diseases: patients with HCV show greater mental impairment, while patients with PBC have greater physical impairment.

Little is known comparing and contrasting quality of life (QoL) in patients with hepatitis C, compared to patients with other liver diseases. We performed two independent prospective cross-sectional studies including 511 and 284 patients with different forms of liver diseases. SF-36 was used in both studies. Fatigue Impact Score, WHO-BREF and Hospital Anxiety and Depression Scale (HADS) were used in either study only. In both studies, HCV-positive patients scored worse in the mental aspects of health-related QoL compared to other liver diseases, except for HBV in one study. Surprisingly, in both studies, quality of life was also significantly impaired in patients with viral clearance after interferon therapy but not after spontaneous clearance. Furthermore, patients with primary biliary cirrhosis showed significantly better mental health but significantly worse physical well-being. Liver diseases differ in their form of impaired QoL. In HCV, this impairment might not always return to normal after treatment-induced viral clearance. This may suggest that HCV either may not be involved in QoL impairment or may induce a process which persists after viral clearance in some patients.

Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target.

BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and many have been identified in heterologous model systems. METHODS: We have developed a stable RNA interference model knocking down EWS-FLI1 in the Ewing sarcoma cell line TC71. Gene expression analyses were performed to study the effect of RNA interference on the genetic signature of EWS-FLI1 and to identify genes that could contribute to tumourigenesis. RESULTS: EWS-FLI1 inhibition induced apoptosis, reduced cell migratory and tumourigenic capacities, and caused reduction in tumour growth. IGF-1 was downregulated and the IGF-1/IGF-1R signalling pathway was impaired. PBK/TOPK (T-LAK cell-originated protein kinase) expression was decreased because of EWS-FLI1 inhibition. We showed that TOPK is a new target gene of EWS-FLI1. TOPK inhibition prompted a decrease in the proliferation rate and a dramatic change in the cell's ability to grow in coalescence. CONCLUSION: This is the first report of TOPK activity in Ewing sarcoma and suggests a significant role of this MAPKK-like protein kinase in the Ewing sarcoma biology.

Factors associated with subluxation in mallet fracture.

Radiographs and medical record of all adult patients with a mallet fracture in three hospitals between 2004 and 2014 were reviewed. International Classification of Diseases, Ninth Revision (ICD-9) codes and text search in radiographic reports were used to identify all acute patients with potential mallet fractures in our institutional database. Manually checking, 392 true mallet fractures were identified among them, 78 had subluxation at the time of diagnosis and 19 had subluxation at a later time point during treatment. Fragment size, fragment displacement, and interval between injury and treatment were associated with initial and late subluxation. Subluxation was not observed when the fracture size was less than 39% of the total articular surface. For each 1% increase in total articular surface involvement in fractures with more than 39% involvement, the risk of subluxation increased by 4% and for each 1% of displacement, the risk of subluxation increased by 4%. LEVEL OF EVIDENCE: IV.

Biochip analysis: status quo.

Biochips are collections of miniaturized test sites (microarrays) arranged on a solid substrate onto which a large number of biomolecules are attached with high density. Like a computer chip performing millions of mathematical operations in a few split seconds, a biochip allows for simultaneous analyses of thousands of biological reactions, such as decoding genes, in a few seconds. Biochip technologies can be applied to numerous fields including genomic, proteomic, and glycomic research, as well as pharmacology and toxicology. However, one of the most common applications is in the determination of gene expression in human cells and tissues. Global gene expression analysis has helped to identify important genes and signalling pathways in human malignant tumors. And there is hope that microarrays will make the step from "the (laboratory) bench to the bedside (of the patient)". Recent studies have indeed revealed that analysis of differential gene expression by microarrays may help to identify subtypes of malignant tumors, that allow a risk stratification of the patients. However, there are several issues that need to be addressed before microarrays may become a tool for routine diagnostics, such as problems with bioinformatic analysis, construction of disease or tissue specific microarrays with only limited numbers of genes of interest, standard operation procedures for tissue preparation to prevent RNA degradation, etc.. In this article, an overview over of the multifarious biochip applications and technologies, its limitations, challenges and future developments is provided.

Evidence for a Na/H Antiporter in Membrane Vesicles Isolated from Roots of the Halophyte Atriplex nummularia.

The ATP-dependent establishment of a positive membrane potential (measured as S(14)CN(-)-accumulation) in membrane vesicles isolated from the roots of Atriplex nummularia Lindl. was not inhibited by NaMes and KMes at concentrations up to 140 millimolar. On the other hand, the formation of DeltapH (measured as (14)C-methylamine accumulation or quenching of quinacrine fluorescence), was depressed by NaMes concentrations as low as 30 millimolar. Supply of NaMes after the DeltapH had been established brought about partial dissipation within 30 seconds. Extent of dissipation of DeltapH increased with NaMes concentration over the range tested (up to 180 millimolar). The H(+)/Na(+) exchange indicated by these results was not due to the creation of a Na(+) diffusion potential. Formation of DeltapH in these vesicles was stable to NO(3) (-) up to 100 millimolar; further, the dissipating effect of Na(+) supply was apparent on a DeltapH formed in the presence of 30 millimolar NO(3) (-). Additional evidence that the origin of the membrane vesicles observed in this investigation was not the tonoplast and was probably the plasmalemma included the vanadate sensitivity of the establishment of the membrane potential.

Studies on H-Translocating ATPases in Plants of Varying Resistance to Salinity : I. Salinity during Growth Modulates the Proton Pump in the Halophyte Atriplex nummularia.

Membrane vesicles were isolated from the roots of the halophyte Atriplex nummularia Lindl. H(+)-translocating Mg(2+)-ATPase activity was manifested by the establishment of a positive membrane potential (measured as SCN(-) accumulation); and also by the establishment of a transmembrane pH gradient (measured by quinacrine fluorescence quenching). H(+)-translocation was highly specific to ATP and was stable to oligomycin. Growing the plants in the presence of 400 millimolar NaCl doubled the proton-translocating activity per milligram of membrane protein and otherwise modulated it in the following ways. First, the flat pH profile observed in non-salt-grown plants was transformed to one showing a peak at about pH 6.2. Second, the lag effect observed at low ATP concentration in curves relating SCN(-) accumulation to ATP concentration was abolished; the concave curvature shown in the double reciprocal plot was diminished. Third, sensitivity to K-2 (N-morpholino)ethanesulfonic acid stimulation was shown in salt-grown plants (about 40% stimulation) but was absent in non-salt-grown plants. Fourth, the KCl concentration bringing about 50% dissipation of ATP-dependent SCN(-) accumulation was 20 millimolar for salt-grown plants and 50 millimolar for non-salt-grown plants. Vanadate sensitivity was shown in both cases. No clear NO(3) (-) inhibition was observed.

Studies on H-Translocating ATPases in Plants of Varying Resistance to Salinity : II. K Strongly Promotes Development of Membrane Potential in Vesicles from Cotton Roots.

Mg(2+)-ATP-dependent H(+)-translocation has been studied in membrane vesicles derived from the roots of Gossypium hirsutum L. var. Acala San Jose 2. Establishment of a positive membrane potential was followed by measuring SCN(-) accumulation; establishment of DeltapH across the vesicle membranes by measuring quinacrine fluorescence quenching. High specificity for ATP was shown, and H(+)-translocation was oligomycin stable. The pH profile for H(+)-translocation showed an optimum at 5.5. The relationship between SCN(-) accumulation and ATP concentration was approximately Michaelian; the apparent K(m) was 0.7 millimolar. K-2-(N-morpholino)ethanesulfonic acid strongly promoted ATP-dependent SCN(-) uptake (up to 180% stimulation). The effect was not given by Na-Mes. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone totally inhibited SCN(-) accumulation, both in the presence and absence of K-2(N-morpholino)ethanesulfonic acid. Vanadate at 200 micromolar inhibited SCN(-) uptake by about 10 to 40% in the absence of K(+), but more strongly in its presence (about 60%). NO(3) (-) at 100 millimolar inhibited initial rate of quinacrine quenching by about 25%. The NO(3) (-) insensitive fraction was activated by K(+); and inhibited by 200 micromolar vanadate to about 40%, provided K(+) was present. Saline conditions during the growth of the plants had no appreciable effect on the observed characteristics of H(+)-translocation.

Sphenoid sinusitis presenting as chronic meningitis.

Sphenoid sinusitis is a frequently misdiagnosed infection. Delay in recognition and treatment carries a very poor prognosis. An unusual case of sphenoid sinusitis mimicking a syndrome of chronic meningitis is presented. This case emphasizes the diagnostic challenge of sphenoid sinusitis which may present only through its complications.

Na/H and k/h antiport in root membrane vesicles isolated from the halophyte atriplex and the glycophyte cotton.

Proton fluxes have been followed into and out of membrane vesicles isolated from the roots of the halophyte Atriplex nummularia and the glycophyte Gossypium hirsutum, with the aid of the DeltapH probe [(14)C]methylamine. Evidence is presented for the operation of Na(+)/H(+) and K(+)/H(+) antiporters in the membranes of both plants. Cation supply after a pH gradient has been set up across the vesicle membrane (either as a result of providing ATP to the H(+)-ATPase or by imposing an artificial pH gradient) brings about dissipation of the DeltapH, but does not depolarize the membrane potential as observed in similar experiments, but in the absence of Cl(-), using the DeltaPsi probe SCN(-). Cation/H(+) exchange is thus indicated. This exchange is not due to nonspecific electric coupling, nor to competition for anionic adsorption sites on the membrane, nor to inhibition of the H(+)-ATPase; coupling of the opposed cation and H(+) fluxes by a membrane component is the most likely explanation. Saturation kinetics have been observed for both Na(+)/H(+) and K(+)/H(+) antiport in Atriplex. Moreover, additive effects are obtained when Na(+) is supplied together with saturating concentrations of K(+), and vice versa, suggesting that separate antiporters for Na(+) and for K(+) may be operating. In the case of both Atriplex and Gossypium evidence was obtained suggesting the presence of antiporters in both plasmalemma and tonoplast.

Intraoperative ultrasonography in cystic brain lesions.

Four neurosurgical patients were operated on under real-time ultrasonographic guidance. Two had cystic tumors which were drained through the unincised dura. In one patient a brain abscess was located intraoperatively by ultrasound after a small craniotomy. In a fourth patient with multiple abscesses, one abscess was drained under ultrasonographic guidance through a previous craniotomy. Using intraoperative ultrasonography the length of the operation can be shortened and normal brain tissue spared. Intraoperative ultrasonography is of special value in cystic lesions which can be drained under ultrasonographic guidance.

The use of antisense mRNA to inhibit the tonoplast H+ ATPase in carrot.

Carrot root cells were transformed with the coding or 5' noncoding regions of the carrot vacuolar H+ ATPase A subunit cDNA cloned in the antisense orientation behind the cauliflower mosaic virus 35S promoter. Bafilomycin-sensitive ATPase, H(+)-pumping, and 14C-O-methyl-glucose uptake activities were specifically inhibited in the tonoplast fractions of mutant cell lines. Protein gel blotting confirmed that the expression of the A subunit was inhibited in the tonoplast fraction, but not in the Golgi fraction. Two-dimensional protein gel blots of total microsomes of wild-type and control transformant cell lines revealed two major immunoreactive polypeptides in the acidic pI range. In contrast, highly purified tonoplast membranes contained only the less acidic polypeptide. Because the less acidic polypeptide was preferentially diminished in the two antisense cell lines, we infer that the antisense constructs specifically blocked expression of a tonoplast-specific isoform of the V-ATPase A subunit in carrot. Regenerated plants containing the antisense constructs exhibited altered leaf morphologies and reduced cell expansion. The altered phenotype was correlated with the presence of the antisense construct.

Diagnostic radiology in wartime.

During the Lebanon War, 1982, over 80% of the wounded were sent from the triage area of the hospital directly to the radiology department. This article reports changes in the working pattern and organization of the department that were instituted for emergency treatment in wartime, and describes radiological examination methods for different organs. Computerized tomography is emerging as the most important diagnostic tool in addition to conventional radiological examinations.