APIC position paper: hepatitis C exposure in the health care setting. Association for Professionals in Infection Control and Epidemiology, Inc

The Association for Professionals in Infection Control and Epidemiology, Inc (APIC), is a multidisciplinary, voluntary, international organization of professionals who practice infection control and the application of epidemiology in all health settings. APIC is an international leader in prevention and control of infection transmission.     

Connexins are expressed in primary brain tumors and enhance the bystander effect in gene therapy

OBJECTIVE: Experimental brain tumor gene therapy with the herpes simplex virus thymidine kinase (HSV-tk) gene has demonstrated that not only HSV-tk transduced but surrounding non-HSV-tk transduced cells are killed when given ganciclovir. This so-called bystander effect has recently been shown to be dependent on connexin-mediated intercellular communication. To assess potential susceptibility to the bystander effect, we examined levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Connexin-26 expression has not previously been studied in primary brain tumors and connexin-43 expression has not been studied in nonastrocytic primary brain tumors. We also attempted to enhance the bystander effect in vitro by overexpressing connexin in tumor cells with high basal levels of connexin expression. METHODS: Western blot analysis and immunohistochemistry were used to determine levels of connexin-26 and connexin-43 expression in a series of primary brain tumors. Wild-type 9L gliosarcoma cells were transfected in vitro with the connexin-43 gene and the HSV-tk gene or the HSV-tk gene alone. The bystander effect of each transfectant was then assessed and compared. RESULTS: Most of the primary brain tumors tested, including low-grade astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, gangliogliomas, meningiomas, and medulloblastomas, showed connexin-26 and connexin-43 expression. Bystander experiments revealed a significant enhancement of the bystander effect in the gliosarcoma cells transfected with connexin-43 and HSV-tk, as compared with gliosarcoma cells transfected with HSV-tk alone. CONCLUSION: Most primary brain tumors express connexin-26 and connexin-43. This suggests that most primary brain tumors may be susceptible to the bystander effect of HSV-tk gene therapy. The bystander effect can be enhanced in vitro by overexpression of connexin-43 in a cell line with a high basal level of connexin-43 expression.     

An unconventional role for cytoplasmic disulfide bonds in vaccinia virus proteins

Previous data have shown that reducing agents disrupt the structure of vaccinia virus (vv). Here, we have analyzed the disulfide bonding of vv proteins in detail. In vv-infected cells cytoplasmically synthesized vv core proteins became disulfide bonded in the newly assembled intracellular mature viruses (IMVs). vv membrane proteins also assembled disulfide bonds, but independent of IMV formation and to a large extent on their cytoplasmic domains. If disulfide bonding was prevented, virus assembly was only partially impaired as shown by electron microscopy as well as a biochemical assay of IMV formation. Under these conditions, however, the membranes around the isolated particles appeared less stable and detached from the underlying core. During the viral infection process the membrane proteins remained disulfide bonded, whereas the core proteins were reduced, concomitant with delivery of the cores into the cytoplasm. Our data show that vv has evolved an unique system for the assembly of cytoplasmic disulfide bonds that are localized both on the exterior and interior parts of the IMV.     

An antagonist for the leukemia inhibitory factor receptor inhibits leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, and oncostatin M

The leukemia inhibitory factor receptor (LIF-R) is activated not only by LIF, but also by cardiotrophin-1, ciliary neurotrophic factor with its receptor, and oncostatin M (OSM). Each of these cytokines induces the hetero-oligomerization of LIF-R with gp130, a signal-transducing subunit shared with interleukin-6 and interleukin-11. The introduction of mutations into human LIF that reduced the affinity for gp130 while retaining affinity for LIF-R has generated antagonists for LIF. In the current study, a LIF antagonist that was free of detectable agonistic activity was tested for antagonism against the family of LIF-R ligands. On cells that express LIF-R and gp130, all LIF-R ligands were antagonized. On cells that also express OSM receptor, OSM was not antagonized, demonstrating that the antagonist is specific for LIF-R. Ligand-triggered tyrosine phosphorylation of both LIF-R and gp130 was blocked by the antagonist. The antagonist is therefore likely to work by preventing receptor oligomerization.     

Adenocarcinoma combined with malignant peripheral nerve sheath tumor of the gallbladder

Adenocarcinoma of the gallbladder combined with a malignant peripheral nerve sheath tumor (MPNST) in the gallbladder in an 81-year-old woman is reported. The resected gallbladder showed two distinct tumor components, the epithelioid type of MPNST and adenocarcinoma with areas of mucin production. Although the immediate postoperative course was uneventful, a pathologic fracture of her right upper femur developed 4 months after the cholecystectomy. The pathology was determined to be a feature of metastatic MPNST rather than of adenocarcinoma. A whole body bone scan revealed multiple metastases, including the left parietal skull, left ninth rib, seventh thoracic vertebra, and right upper third of the femur. Despite cholecystectomy and postoperative irradiation therapy, she died 6 months after diagnosis of the tumor. Without an autopsy the primary site of the MPNST was unknown. We found that the prognosis was very poor in patients with distal metastatic MPNST, especially in older patients.     

Iron management in end-stage renal disease

One of the important components of successful anemia therapy in patients with end-stage renal disease (ESRD) treated with recombinant human erythropoietin is the maintenance of adequate available iron. To accomplish this task, iron status must be serially monitored and supplemental iron administered as required. Among nonuremic subjects, the body's iron supply is tightly conserved, and iron deficiency usually develops only when chronic blood loss occurs. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the body's storage of iron, and perhaps a deficit in intestinal iron absorption. Detecting iron deficiency in these patients can be difficult because of the inaccuracy of available diagnostic tests. The goals of iron therapy in ESRD include the prevention of iron deficiency by chronically supplementing iron, and the prompt treatment of overt iron deficiency. Oral iron supplements are inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit their effectiveness. Intravenous iron supplements have a greater efficacy then oral iron, which must be weighed against the small risk of allergic reactions. We present strategies for using the various diagnostic tests and treatment modalities to effectively manage iron supply for predialysis, hemodialysis, and peritoneal dialysis patients.     

Patient-specific predictions for clinical decision-making

There are many ways in which clinicians make decisions regarding therapy for an individual patient. Invariably, the decision is supplemented by collateral information which is obtained from clinical trials. Prospective and retrospective clinical studies take an unnecessary adversarial position but each method has its place. Parametric survival analysis can produce patient-specific predictions of an event of interest for an individual patient based on the risk factor profile of that patient, and these methods are just as applicable to prospective clinical studies as they are to retrospective clinical studies. Parametric survival analysis can estimate the distribution of time to an event, estimate the phases of hazard (instantaneous risk of the event), determine risk factors associated with the event in each of the identified phases of risk, predict the time-related probability of an event for a specific patient based on his or her risk factor profile, and by risk adjustment compare the effectiveness of different therapies.     

The non heart-beating donor

Given the shortage of donor kidneys for transplantation, we have focused on the use of non heart-beating (NHB) donor kidneys since 1982. The major drawback for the use of NHB donor kidneys is the inherent possibility of severe ischaemic damage leading to primary non function. Thus viability assessment of ischaemically damaged kidneys is crucial, and, therefore, a machine perfusion programme was reinstituted in 1993. Machine perfusion (MP) enables viability assessment through analysis of perfusion characteristics and measurement of enzyme release into the perfusate. Of the last 100 consecutive MP NHB donor kidneys, 71 kidneys were transplanted and 29 kidneys were discarded. Nine kidneys started functioning immediately, 51 kidneys showed delayed function and 11 kidneys never functioned. When analysing in retrospect different parameters for viability assessment, only alpha-GST, an enzyme specific for damage of proximal tubular cells within the kidney, could discriminate between functioning and non-functioning kidneys. With this promising viability assessment, the large NHB donor potential and the good transplant results, we recommend the use of these donors.     

Bilateral elastofibroma: a case report and review of the literature

Elastofibroma, or elastofibroma dorsi as it was first described, is an uncommon tumor-like process that characteristically appears as an ill-defined mass in the infrascapular region of elderly patients. This lesion can occur bilaterally and may appear asynchronously. The occurrence of elastofibroma in other anatomic sites has been reported, although with much less frequency. Elastofibromas display typical diagnostic histologic, cytologic, and electron microscopic features. The use of magnetic resonance imaging can lead to a presumptive diagnosis in elderly individuals with suprascapular lesions. It is important to differentiate this lesion from other soft-tissue lesions, such as sarcomas and desmoid tumors. This study presents a case of bilateral elastofibromas in a 72-year-old man and a review of the literature.