A case of recurrent hepatic haemangioendothelioma.

Hepatic haemangioendothelioma is a rare (1:1,000,000) mesenchymal tumour of the liver of vascular origin. Metastatic malignancies, other primary liver tumours and cholangiocarcinomas all have significantly worse prognoses and may mimic hepatic haemangioendothelioma. Hence, careful pathological assessment with appropriate tumour markers and immunohistochemistry are essential. We present a rare case of recurrence of hepatic haemangioendothelioma after 10 years post-hemihepatectomy. Surgical approaches include liver resection, liver transplantation and ablative techniques with chemotherapy and radiotherapy reserved for patients where a surgical approach is not possible. Hepatic haemangioendothelioma has an unpredictable course that is generally indolent and it is associated with a significantly better long-term survival. Consequently, it is important that these tumours are recognised and the approach to the diagnosis should be methodical. Owing to the protracted course of the disease, a prolonged duration of surveillance and an aggressive approach towards disease recurrence are essential for long-term survival.

Predictors for 30-day mortality and complications following radiologically inserted gastrostomies: a single centre, large cohort review.

AIM: To measure the 30-day mortality and delayed complication rates following radiologically inserted gastrostomy (RIG) placement and determine the predictive risk factors for 30-day mortality and delayed complications to aide pre-procedure informed consent. MATERIALS AND METHODS: Retrospective analysis was undertaken of RIG insertions between July 2012 and August 2017 at a single tertiary centre, which included 373 patients (56% male; median age: 65 years, range: 19-92 years). Data were collected from electronic databases on patient demographics, RIG indication, all-cause mortality, complication rates, patient co-morbidities, and biochemical/haematological parameters. Multivariate analysis was performed to identify predictive risk factors for complications and mortality. RESULTS: The RIG procedural success rate was 97.9%. The overall 30-day mortality rate was 7.8%; associated with pre-procedural haemoglobin <130 g/l in men (p=0.030, odds ratio [OR] 23.38), white cell count >11×109/l (p=0.001, OR 4.18), C-reactive protein >10 mg/l (p=0.003, OR 10.10) and international normalised ratio (INR) >1.2 (p=0.03, OR 4.63). Inpatient RIG referrals were associated with 10% 30-day mortality; compared to 1.1% for outpatients (p=0.028, OR 9.51). The incidence of immediate and delayed complications was 2.4% and 42.1%, respectively. Neuromuscular disease was associated with gastrostomy dislodgement (p=0.0001, OR 4.99) and fracture (p=0.0009, OR 13.45), cerebrovascular disease with gastrostomy dislodgement (p=0.009, OR 2.51), cardiovascular disease with sepsis 30-days post-RIG (p=0.02, OR 2.94), and diabetes mellitus with gastrostomy dislodgement (p=0.0001, OR 29.45), fracture (p=0.027, OR 5.63) and stoma site infections (p=0.0003, OR 7.16). CONCLUSION: RIG 30-day mortality was significantly associated with inpatient procedures compared to outpatient, and a range of biochemical/haematological parameters that suggest infection pre-intervention. It is advised that the markers of infection and catabolism are investigated pre-intervention, which may reduce mortality and complication rates.

Pulmonary complications in the non-HIV immunocompromised patient.

The incidence of non-HIV immunocompromised patients is increasing. This is primarily due to improved immunosuppressive regimes for autoimmune diseases and also increases in stem cell transplantation. Pulmonary complications are a major cause of morbidity and mortality in these patients. Imaging is frequently used to assess these complications and to streamline therapies, as microbiological and/or pathological diagnosis can often be difficult, invasive, or protracted. This review provides the reader with a structured approach to interpret the imaging findings and differentiate between different infective and non-infective complications in these patients.

Management benefits and safety of computed tomography in patients undergoing extracorporeal membrane oxygenation therapy: experience of a single centre.

AIM: To evaluate the benefits and logistical safety of computed tomography (CT) imaging in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy in a single institution. MATERIALS AND METHODS: Over a period of 25 months, 134 patients (80 neonates, 19 children, and 35 adults) underwent ECMO therapy at this institution. The imaging of these patients was reviewed to identify patients who had undergone CT imaging whilst on ECMO. Patient notes were retrospectively reviewed. CT findings and subsequent decisions were analysed to assess the benefit of CT imaging. Complications arising due to the logistics of performing the scan were analysed to assess the safety of performing CT in ECMO patients. RESULTS: Of 134 patients, 14 (10%) had a total of 15 CT examinations whilst undergoing ECMO therapy. Indications for CT included new neurology, increased respiratory demand, and increasing requirement for high ECMO flows. There were no major complications and two minor complications associated with the logistics of performing a CT examination on an ECMO patient. Significant findings resulted from 73.3% (11/15) of the CT examinations, and in all 15 examinations information was provided that was used in making further management decisions, including, in some cases, withdrawal of ECMO therapy. CONCLUSION: With an experienced team, CT imaging of patients on ECMO can be performed safely. CT provides valuable information for subsequent management of patients undergoing ECMO therapy.

Muc4/sialomucin complex in the mammary gland and breast cancer.

MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, characterized by mucin tandem repeat domains and a transmembrane domain which associates it with the cell plasma membrane. Although MUC4 is encoded by a single gene, it is produced by epithelial cells as a heterodimer through a proteolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protective mechanism(s) may be highjacked by some carcinomas, such as those of the breast, to increase tumor progression. Two mechanisms are proposed to contribute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-recognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bind the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Expression of MUC4 in mammary gland is repressed by posttranscriptional mechanisms involving basement membrane and TGF-beta, which are relieved during pregnancy to permit secretion of MUC4 into milk. These mechanisms are also abrogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.

Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor.

Overexpression of the membrane mucin MUC4/Sialomucin complex (SMC) has been observed during malignant progression of mammary tumors in both humans and rats, suggesting that deregulation of MUC4/SMC expression might facilitate development of these malignancies. As previously reported, overexpression of SMC results in suppression of both cell adhesion and immune killing of tumor cells. SMC also acts as a ligand for ErbB2/Neu, modulating phosphorylation of the receptor tyrosine kinase in the presence and absence of heregulin. The present studies investigated the effect of Muc4/SMC up-regulation on primary tumor growth using a tetracycline-inducible SMC expression system in a xenotransplanted tumor model. SMC up-regulation provoked rapid growth of transfected A375 melanoma in nude mice. Up-regulation of SMC, however, did not significantly increase proliferation of A375 cells in vitro. Instead, a strong suppression of apoptosis was observed in situ in SMC-overexpressing tumors. These data suggest that Muc4/SMC expression promotes tumor growth in vivo at least in part via suppression of tumor cell apoptosis. Importantly, reduction of apoptosis was also observed in vitro, indicating that anti-apoptotic effect of SMC is independent of tumor-host interactions. These findings strongly suggest that SMC up-regulation alters intracellular signaling to favor cell survival, providing for the first time evidence for the regulation of programmed cell death by a gene of the MUC family.

Multiple facets of sialomucin complex/MUC4, a membrane mucin and erbb2 ligand, in tumors and tissues (Y2K update).

Sialomucin complex (SMC, MUC4) is a high Mr glycoprotein heterodimer, composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. ASGP-2 contains two EGF-like domains and acts as an intramembrane ligand for the receptor tyrosine kinase ErbB2. Transfection studies with SMC DNAs showed that SMC expression could markedly reduce both cell-cell and cell-matrix interactions in vitro and increase the growth of primary tumors and the formation of metastatic foci of human A375 melanoma cells as xenotransplants in nude mice, possibly through the ability to suppress apoptosis. SMC is expressed in most vulnerable epithelia as a protective agent, which is found in both membrane and soluble forms at luminal surfaces and secreted into fluids such as milk and tears. SMC appears to be constitutively expressed by most accessible epithelia, notable exceptions being the mammary gland and uterine luminal epithelium, in which it is tightly regulated during pregnancy. Down-regulation at the luminal uterine surface appears necessary for blastocyst implantation. TGF-b is a potent repressor of SMC expression in the mammary gland and uterus, though by different mechanisms. These combined results suggest that SMC has multiple functions in epithelia and is tightly regulated in those tissues where its special functions are required.

Mycophenolic acid does not inhibit protein glycosylation in T lymphocytes.

BACKGROUND: Mycophenolic acid inhibits guanosine nucleotide synthesis and has been shown to be a potent inhibitor of lymphocyte proliferation as well as being effective at decreasing the incidence of graft rejection. Guanosine nucleosides are essential for protein glycosylation and many cell surface proteins including adhesion molecules, which are important for graft infiltration and rejection, are glycoproteins. There have been conflicting reports concerning the ability of MPA to interfere with glycosylation in lymphoid cells. Therefore, the purpose of this study was to investigate the effects of MPA on cell surface protein glycosylation in lymphoid cells. METHODS: Cells were cultured in the presence of increasing concentrations of MPA for different lengths of time and stained with fluorescent-labelled lectins specific for either mannose or fucose residues on glycoproteins. Analysis was then performed by flow cytometry. RESULTS: MPA treatment had no effect on the binding of either fucose or mannose-specific lectins to Con A stimulated human PBLs and rat lymph node lymphocytes or to a CEMC7a T cell line. CONCLUSION: The results show that, contrary to previous reports, MPA does not affect cell surface glycosylation in T cells using T cells from different sources of both human and non-human origin.

Value-based formulas for purchasing. Loyalty renaissance: the rebirth of loyalty in health care.

As more consumers join managed care organizations, the personal bond between patient and physician or medical group has been transformed into an economic relationship driven chiefly by the price of health care services. Managed care organizations now face the same pressures as the airline and retail industries: To gain and retain client loyalty through product differentiation and consistently high levels of service. How do managed health care plans create and maintain loyalty among their members? What is the value proposition that consumers will respond to in this era of managed care? Discussion will focus on the consumer as the critical variable in the economic model of a health care system and how the consumer will impact the continued evolution of managed care.

Purification of a maize dehydrin protein expressed in Escherichia coli.

A maize dehydrin protein (Dhn1) containing 167 amino acids with a predicted molecular weight of 17.0 kDa was produced in the Escherichia coli overexpression strain BL21 (DE3)pLysS. Site-directed mutagenesis was used to construct a plasmid with a protein coding region corresponding exactly to the original cDNA. Protein production was induced by IPTG. Dhn1 was enriched from total soluble protein by heat-fractionation and centrifugation and then purified by sequential cation exchange and hydrophobic interaction chromatography. The purified protein was visualized by SDS-PAGE and immunoblot analysis using a polyclonal antibody to the dehydrin consensus region. Expression in E. coli resulted in approximately 1.2 mg of purified protein per liter of induced culture.

Management of upper respiratory tract infections by telephone.

We surveyed Utah general internists (N = 134) regarding their attitudes toward and practices associated with telephone management of upper respiratory tract infections. The questionnaire contained 3 case vignettes--viral upper respiratory tract infection, streptococcal pharyngitis, and acute infectious epiglottitis--and a series of questions were asked about telephone diagnosis, management preferences (clinic versus telephone), and telephone management practices. The 53 respondents (40%) were able to make important diagnostic distinctions about upper respiratory tract infections from a written vignette. As the likelihood of a complicated or serious condition increased, patients would be appropriately triaged for clinical evaluation. Most internists would make a written record of the telephone conversation. Only 1 internist of the 53 would charge for telephone management.

Control and evaluation of high-frequency jet ventilation: mechanical lung model.

Ventilation systems that operate at high-frequency and deliver small volumes have the potential to provide adequate alveolar ventilation without excessive pulmonary pressures. One way of producing high-frequency ventilation is by use of jet bursts of an input gas through a cannula controlled by a solenoid valve. This high-frequency jet ventilation has yet to be quantitatively analysed for optimal clinical use. From an analysis of the jet-producing device, we obtained a quantitative relationship which allowed us to predict the gas volume of a jet burst (Vjet) from the driving pressure (Pd), and the jet duration (tI). The device was applied to a mechanical lung model (a tube attached to an elastic bag corresponding to the lung airway and alveolar space). We examined how the control variables of the jet ventilation system changed the bag (alveolar) volume with respect to Vjet, the volume of entrained gas, and the volume of shunted gas. Using a nitrogen washout analysis, we evaluated the operating lung volume, effective dead-space volume (Veds), and effective ventilation rate (Veff). We found that Veds is independent of the individual effects of jet cycle frequency, duty cycle, cannula diameter, and entrainment fraction. While Veds was not affected significantly by the shape of the airway, it did depend on the distance of the jet cannula tip to the ventilated bag (or alveolar region) and on the tidal volume.