Progression of neurovisceral storage disease with supranuclear ophthalmoplegia following orthotopic liver transplantation

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver

Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial

Background: Shoulder complaints are common in primary care and have unfavourable long term prognosis. Our objective was to evaluate the clinical effectiveness of manipulative therapy of the cervicothoracic spine and the adjacent ribs in addition to usual medical care (UMC) by the general practitioner in the treatment of shoulder complaints. Methods: This economic evaluation was conducted alongside a randomized trial in primary care. Included were 150 patients with shoulder complaints and a dysfunction of the cervicothoracic spine and adjacent ribs. Patients were treated with UMC (NSAID's, corticosteroid injection or referral to physical therapy) and were allocated at random (yes/no) to manipulative therapy (manipulation and mobilization). Patient perceived recovery, severity of main complaint, shoulder pain, disability and general health were outcome measures. Data about direct and indirect costs were collected by means of a cost diary. Results: Manipulative therapy as add-on to UMC accelerated recovery on all outcome measures included. At 26 weeks after randomization, both groups reported similar recovery rates (41% vs. 38%), but the difference between groups in improvement of severity of the main complaint, shoulder pain and disability sustained. Compared to the UMC group the total costs were higher in the manipulative group ((sic)1167 vs.(sic)555). This is explained mainly by the costs of the manipulative therapy itself and the higher costs due sick leave from work. The cost effectiveness ratio showed that additional manipulative treatment is more costly but also more effective than UMC alone. The cost-effectiveness acceptability curve shows that a 50%-probability of recovery with AMT within 6 months after initiation of treatment is achieved at (sic)2876. Conclusion: Manipulative therapy in addition to UMC accelerates recovery and is more effective than UMC alone on the long term, but is associated with higher costs

Does knowledge of cancer diagnosis affect quality of life? A methodological challenge

BACKGROUND: As part of an assessment of quality of life in lung cancer patients an investigation was carried out to examine whether the knowledge of their diagnosis affected their quality of life. METHODS: Every patient in a defined geographical area with a potential diagnosis of lung cancer was interviewed at first consultation and after a definitive treatment has been given. Quality of life was assessed using three standard measures: the Nottingham Health Profile (NHP), the EORTC quality of life questionnaire (QLQ-C30) and its lung cancer supplementary questionnaire (QLQ-LC13). Comparison was made in quality of life scores between patients who knew their cancer diagnosis and those who did not. RESULTS: In all, 129 lung cancer patients were interviewed. Of these, 30 patients (23%) knew and 99 (78%) did not know their cancer diagnosis at the time of baseline assessment. The patient groups were similar in their characteristics except for age (P = 0.04) and cell type (P < 0.0001). Overall, there were no significant differences between these two groups with regard to their scores on the three instruments used. A major finding was that both group scored almost the same on emotional reactions (P = 0.8) and social isolation (P = 1.0) as measured by the NHP, and emotional (P = 0.7) and social functioning (P = 1.0) as measured by the EORTC QLQ-C30. In addition there were no significant differences in patients' symptom scores between those who knew their diagnosis and those who did not, nor did any consistent pattern emerge. The only significant difference was for sleep difficulties (P = 0.02). CONCLUSION: The findings suggest that the knowledge of cancer diagnosis does not affect the way in which patients respond to quality of life questionnaires

Risky use of alcohol, drugs and cigarettes in a psychosis unit: a 1 1/2 year follow-up of stability and changes after initial screening

<p>Abstract</p> <p>Background</p> <p>Co-morbidity with substance use disorders negatively influences overall functioning in patients with psychosis. However, frequencies and courses of risky use of alcohol, drugs and cigarettes are rarely investigated in patients at psychosis units.</p> <p>The purpose of this study is to describe the use of alcohol, drugs and cigarettes in patients at a psychosis unit over a 1 1/2 year period after them having taken part in a screening investigation including a feed-back of the results to personnel. Relationships with sex and age are also described.</p> <p>Methods</p> <p>The patients' use of the substances was examined at baseline and at follow-up using three self-reporting instruments: Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT) and Fagerstrom Test for Nicotine Dependence (FTND).</p> <p>Results</p> <p>One hundred and eighty-six patients out of 238 at baseline (78 percent) took part in the follow-up. Total AUDIT score decreased in women. Older men more often developed a risky alcohol use. Older women tended to reduce their risky drug habits. On a group level the habits mostly were stable, but 11 percent changed their alcohol habits and 15 percent changed their smoking habits from risky to no/low risky use, or vice versa. Nine percent changed their drug habits, predominantly from risky to no/low risky use.</p> <p>Conclusion</p> <p>A more active approach towards alcohol, drug and smoking habits in psychosis units would probably be beneficial.</p

Primary mediastinal B-cell lymphoma: detection of BCL2 gene rearrangements by PCR analysis and FISH

Primary mediastinal large B-cell lymphoma (PMBCL) has a characteristic clinical presentation, morphology, and immunophenotype, representing a clinically favorable subgroup of diffuse large B-cell lymphoma (DLBCL). By gene expression profiling (GEP), PMBCL shares features with classical Hodgkin lymphoma (cHL). Of further interest, BCL6 gene mutations and BCL6 and/or MUM1 expression in a number of PMBCLs have supported an activated B-cell (ABC) origin. Several studies, including GEP, have failed to detect BCL2 gene rearrangements (GRs) in PMBCL. An index case of t(14; 18)+ PMBCL prompted our study of the incidence of BCL2 GRs in PMBCL by polymerase chain reaction (PCR)/fluorescence in situ hybridization (FISH) analyses and its possible clinical impact. Twenty-five retrospectively identified, well-defined PMBCLs (five with cytogenetics) from three institutions were analyzed for a BCL2 GR by PCR/FISH analyses. The formalin-fixed, paraffin-embedded tissue blocks of 24 available cases were also analyzed by BCL2 immunohistochemistry (IHC). Of the five with cytogenetics, two had a t(14; 18) (q32; q21). Of the 25 analyzed by PCR, 2 had no amplifiable DNA (aDNA), including 1 t(14; 18)+ case. Of those with aDNA, two showed a BCL2 GR; by FISH analysis, three demonstrated a BCL2 GR. BCL2 protein expression by IHC analysis was variably detected in 21 out of 24 (strongly, uniformly expressed: 6, including all with a t(14; 18) or a BCL2 gene rearrangement; moderately weakly expressed in a subset of the malignant cells: 15). Available clinical follow-up of this BCL2+ subset showed a similar course to the other PMBCL cases. Our results imply that a subset of PMBCL [(4 out of 24 analyzed) in our series] may be of GC origin. A larger study is necessary to determine any clinical significance

Baryonic Popcorn

In the large N limit cold dense nuclear matter must be in a lattice phase. This applies also to holographic models of hadron physics. In a class of such models, like the generalized Sakai-Sugimoto model, baryons take the form of instantons of the effective flavor gauge theory that resides on probe flavor branes. In this paper we study the phase structure of baryonic crystals by analyzing discrete periodic configurations of such instantons. We find that instanton configurations exhibit a series of "popcorn" transitions upon increasing the density. Through these transitions normal (3D) lattices expand into the transverse dimension, eventually becoming a higher dimensional (4D) multi-layer lattice at large densities. We consider 3D lattices of zero size instantons as well as 1D periodic chains of finite size instantons, which serve as toy models of the full holographic systems. In particular, for the finite-size case we determine solutions of the corresponding ADHM equations for both a straight chain and for a 2D zigzag configuration where instantons pop up into the holographic dimension. At low density the system takes the form of an "abelian anti-ferromagnetic" straight periodic chain. Above a critical density there is a second order phase transition into a zigzag structure. An even higher density yields a rich phase space characterized by the formation of multi-layer zigzag structures. The finite size of the lattices in the transverse dimension is a signal of an emerging Fermi sea of quarks. We thus propose that the popcorn transitions indicate the onset of the "quarkyonic" phase of the cold dense nuclear matter.Comment: v3, 80 pages, 18 figures, footnotes 5 and 7 added, version to appear in the JHE

Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H⁺ secretion

The cystic fibrosis (CF) airway surface liquid (ASL) provides a nutrient rich environment for bacterial growth including elevated glucose, which together with defective bacterial killing due to aberrant HCO3− transport and acidic ASL, make the CF airways susceptible to colonisation by respiratory pathogens such as Pseudomonas aeruginosa. Approximately half of adults with CF have CF related diabetes (CFRD) and this is associated with increased respiratory decline. CF ASL contains elevated lactate concentrations and hyperglycaemia can also increase ASL lactate. We show that primary human bronchial epithelial (HBE) cells secrete lactate into ASL, which is elevated in hyperglycaemia. This leads to ASL acidification in CFHBE, which could only be mimicked in non-CF HBE following HCO3− removal. Hyperglycaemia-induced changes in ASL lactate and pH were exacerbated by the presence of P. aeruginosa and were attenuated by inhibition of monocarboxylate lactate-H+ co-transporters (MCTs) with AR-C155858. We conclude that hyperglycaemia and P. aeruginosa induce a metabolic shift which increases lactate generation and efflux into ASL via epithelial MCT2 transporters. Normal airways compensate for MCT-driven H+ secretion by secreting HCO3−, a process which is dysfunctional in CF airway epithelium leading to ASL acidification and that these processes may contribute to worsening respiratory disease in CFRD

Transcriptional Profiling of Bacillus anthracis Sterne (34F2) during Iron Starvation

Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F2) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study

Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Inflammatory bowel disease (IBD) is used to describe a state of idiopathic, chronic inflammation of the gastrointestinal tract. The two main phenotypes of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The major cause of IBD-associated mortality is colorectal cancer. Although both host-genetic and exogenous factors have been found to be involved, the aetiology of IBD is still not well understood. In this study we characterized thirteen <it>Escherichia coli </it>strains from patients with IBD by comparative genomic hybridization employing a microarray based on 31 sequenced <it>E. coli </it>genomes from a wide range of commensal and pathogenic isolates.</p> <p>Results</p> <p>The IBD isolates, obtained from patients with UC and CD, displayed remarkably heterogeneous genomic profiles with little or no evidence of group-specific determinants. No IBD-specific genes were evident when compared with the prototypic CD isolate, LF82, suggesting that the IBD-inducing effect of the strains is multifactorial. Several of the IBD isolates carried a number of extraintestinal pathogenic <it>E. coli </it>(ExPEC)-related virulence determinants such as the <it>pap</it>, <it>sfa</it>, <it>cdt </it>and <it>hly </it>genes. The isolates were also found to carry genes of ExPEC-associated genomic islands.</p> <p>Conclusions</p> <p>Combined, these data suggest that <it>E. coli </it>isolates obtained from UC and CD patients represents a heterogeneous population of strains, with genomic profiles that are indistinguishable to those of ExPEC isolates. Our findings indicate that IBD-induction from <it>E. coli </it>strains is multifactorial and that a range of gene products may be involved in triggering the disease.</p