HIS/BUI: A Conceptual Model for Bottom-Up Integration of Hospital Information Systems

Many successful applications of information systems have been introduced and implemented in hospitals. However, the integration of these applications into a cohesive hospital-wide information system has proved to be more complicated to develop and difficult to accomplish than expected. This paper introduces HIS/BUI, a framework for bottom-up integration of hospital information systems, and demonstrates its application through a real-life case scenario. The scope of the proposed framework is the integration of heterogeneous clinical, administrative, and financial information elements of a hospital into a unified system environment. Under the integrated architecture, all existing local applications are preserved and interconnected to an information hub that serves as a central medical and administrative data warehouse.     

Solid pseudopapillary pancreatic tumor in pregnancy. A case report

BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm, occurring predominantly in young African American women. Tumor growth, which is typically slow, may be accelerated during pregnancy secondary to the influence of progesterone. CASE: We report a rare case of an 8-cm SPT in the head of the pancreas presenting as hyperemesis gravidarum during pregnancy. In contrast to previous case reports, surgical resection of the tumor at 16 weeks' gestation, although successful, did not ameliorate the patient's abdominal pain, nausea or vomiting. With intravenous nutritional support, she delivered a healthy infant near term. CONCLUSION: SPT may present as hyperemesis gravidarum. Patients with refractory hyperemesis gravidarum should be evaluated for thyroid disease, gastroesophageal reflux, cholestasis and pancreatitis. If these more common etiologies are excluded, then one may consider SPT in the differential diagnosis, particularly in African American patients. SPT may grow during pregnancy due to progesterone responsiveness. Surgical resection during pregnancy is possible without harmful fetal effects but may not correct gastrointestinal dysfunction during pregnancy.     

c-Cbl is a critical modulator of the Ron tyrosine kinase receptor

Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the multifunctional docking site as well as to a juxtamembrane tyrosine autophosphorylation site. c-Cbl recruitment to these two sites results in polyubiquitylation of Ron molecules, which are subsequently sorted for endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl are found also in physical complexes that include Grb2, these associations are insufficient for productive ubiquitylation of Ron. Our results shed light on the mechanism of receptor desensitization mediated by c-Cbl and its binding partner Grb2.     

Extent of disease burden determined with magnetic resonance imaging of the bone marrow is predictive of survival outcome in patients with multiple myeloma

BACKGROUND:

Multiple myeloma (MM) remains an incurable cancer. Treatment often is initiated at the time patients experience a progressive increase in tumor burden. The authors of this report investigated magnetic resonance imaging of the bone marrow (BM‐MRI) as a novel approach to quantify disease burden and validated a staging system by correlating BM‐MRI with common clinical and laboratory parameters.

METHODS:

The extent of bone marrow involvement was evaluated by BM‐MRI. Clinical and laboratory parameters were assessed in patients with active MM, and correlations between variables were assessed statistically. Bone marrow involvement by BM‐MRI was defined as stage A (0%), stage B (<10%), stage C (10%‐50%), and stage D (>50%).

RESULTS:

In total, 170 consecutive patients were evaluated (77 women and 93 men), including 144 patients who had active MM. The median age was 61 years (age range, 35‐83 years). Advance stage disease (stage >I) based on Durie‐Salmon (DS) staging or International Staging System (ISS) criteria was observed in 122 patients (84%) and 77 patients (53%), respectively. Lytic bone disease was noted in 120 patients (83%). There was a significant association between BM‐MRI involvement and DS stage (P = .0006), ISS stage (P = .0001), the presence of lytic bone disease (P < .0001) and mean β‐2 microglobulin levels (P < .0001). Among the patients with previously untreated MM, there was a significant association between BM‐MRI stage and overall survival (OS) (univariate P = .013; multivariate P = .045). Plasmacytosis on bone marrow biopsy at diagnosis was not predictive of OS (P = .91).

CONCLUSIONS:

BM‐MRI is a novel approach for quantifying disease burden in patients with MM. The current investigation in a large cohort of nontransplantion MM patients demonstrated that the extent of bone marrow involvement determined by BM‐MRI correlates accurately with other conventional parameters of disease burden and can independently predict survival in patients with MM at the time of initial diagnosis. Cancer 2010. © 2010 American Cancer Society.     

Membrane-Pore Forming Characteristics of the Bordetella pertussis CyaA-Hemolysin Domain

Previously, the 126-kDa Bordetella pertussis CyaA pore-forming/hemolysin (CyaA-Hly) domain was shown to retain its hemolytic activity causing lysis of susceptible erythrocytes. Here, we have succeeded in producing, at large quantity and high purity, the His-tagged CyaA-Hly domain over-expressed in Escherichia coli as a soluble hemolytically-active form. Quantitative assays of hemolysis against sheep erythrocytes revealed that the purified CyaA-Hly domain could function cooperatively by forming an oligomeric pore in the target cell membrane with a Hill coefficient of ~3. When the CyaA-Hly toxin was incorporated into planar lipid bilayers (PLBs) under symmetrical conditions at 1.0 M KCl, 10 mM HEPES buffer (pH 7.4), it produced a clearly resolved single channel with a maximum conductance of ~35 pS. PLB results also revealed that the CyaA-Hly induced channel was unidirectional and opened more frequently at higher negative membrane potentials. Altogether, our results first provide more insights into pore-forming characteristics of the CyaA-Hly domain as being the major pore-forming determinant of which the ability to induce such ion channels in receptor-free membranes could account for its cooperative hemolytic action on the target erythrocytes.     

ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy

Clinical and experimental data suggest that ErbB-4, a member of the epidermal growth factor receptor family, may have a role in cancer progression and response to treatment. We found recently, using a retrospective clinical analysis, that expression of ErbB-4 receptor is correlated with metastatic potential and patient survival in non-small-cell lung cancer (NSCLC). The purpose of this work was to correlate the expression of the ErbB-4 and lung cancer cells growth in vitro and in vivo and to determine the therapeutic potential of a monoclonal antibody to ErbB-4 against lung cancer. For this aim, we ectopically expressed ErbB-4 in a human NSCLC cell line that did not express the ErbB-4 protein. Overexpression of ErbB-4 produced a constitutively activated ErbB-4 receptor. The transfected ErbB-4 positive clones showed an increased cell proliferation in vitro and in vivo in comparison with parental ErbB-4 negative cells and with the cells transfected by neomycin-resistant gene. A monoclonal antibody to ErbB-4 showed both an inhibitory effect on growth rate and an increasing apoptotic rate in the cells expressing ErbB-4. The results of the current study provide evidence that ErbB-4 plays a significant role in human lung cancer and may serve as a molecular target for anticancer therapy.     

Functional significance of the highly conserved Glu in the putative pore-forming helix 3 of the Bordetella pertussis haemolysin toxin

Adenylate cyclase-haemolysin toxin (CyaA) is a virulence factor secreted from the etiologic agent of whooping cough, Bordetella pertussis. Previously, the haemolysin or pore-forming domain (CyaA-PF) has been shown to cause cell lysis of sheep erythrocytes independently, and the predicted helix 3_(570−593) within the PF-hydrophobic stretch could be a pore-lining constituent. Here, a plausible involvement in haemolytic activity of polar or charged residues (Glu⁵⁷⁰, Gln⁵⁷⁴, Glu⁵⁸¹, Ser⁵⁸⁴ and Ser⁵⁸⁵) lining the hydrophilic side of CyaA-PF helix 3 was investigated via single-alanine substitutions. All the 126-kDa mutant proteins over-expressed in Escherichia coli were verified for toxin acylation as the results are corresponding to the wild-type toxin. When haemolytic activity of E. coli lysates containing soluble mutant proteins was tested against sheep erythrocytes, the importance of Glu⁵⁷⁰, which is highly conserved among the pore-forming RTX cytotoxin family, was revealed for pore formation, conceivably for a general pore-lining residue involved in ion conduction.     

Bone grafting in total hip replacement for acetabular protrusion: A review of 11 operations

In 11 total hip replacement operations performed on nine patients with acetabular protrusion, the deficient acetabulum was reinforced with a bone graft from the femoral head in ten operations and in one from the greater trochanter and the femoral medullary canal. Acetabular meshes were used in two operations and a fine wire mesh in one.

At follow-up, averaging 18 (8-28) months postoperatively, a solid bone socket for the acetabular component had formed in all hips without evidence of loosening or infection.