Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Acute Renal Failure after Lung Transplantation: Incidence, Predictors and Impact on Perioperative Morbidity and Mortality

The incidence, predictors and clinical significance of acute renal failure (ARF) after lung transplantation are not well described. We retrospectively collected data on 296 patients transplanted at our center between April 1992 and December 2000; follow-up was extended until December 2002. Patients were initially divided into two groups: ARF (doubling of baseline creatinine within 2 weeks after surgery) and NoARF. The ARF group was subdivided into ARFD (dialyzed) and ARFnD (not dialyzed). The incidence of ARF was 56% (166/296), but most cases were ARFnD (n = 143). Independent predictors of ARFD (n = 23) were: baseline GFR (OR 0.98, CI 0.96-0.99, p = 0.012), pulmonary diagnosis other than COPD (OR 6.80, CI 1.5-30.89, p = 0.013), mechanical ventilation > 1 d (OR 6.16, CI 1.70-22.24, p = 0.006) and parenteral amphotericin B use (OR 3.04, CI 1.03-8.98, p = 0.045). Both ARFnD and ARFD were associated with longer duration of mechanical ventilation, increased hospital stay and increased early mortality. One-year patient survival was 92.3%, 81.8% and 21.7% in the NoARF, ARFnD and ARFD groups, respectively (p < 0.0001). After controlling for important covariates, ARFD remained associated with an increased hazard of dying (HR 6.77, CI 4.00-11.44, p < 0.0001). In conclusion, ARF occurs commonly after lung transplantation and affects important clinical outcomes, especially when dialysis is required.     

Periocular involvement in cutaneous leishmaniasis

OBJECTIVE: Although cutaneous leishmaniasis (CL) occurs mostly in the facial area, periocular involvement accounts for 2-5% of the facial lesions. CL lesions localized in the periocular region can easily be confused with various other diseases. The aim of this study was to examine the frequency of periocular involvement in CL in the Cukurova region of Turkey, as well as the clinical characteristics, diagnosis and methods of treatment of this disease. METHODS: Between December 1998 and December 2004, patients who were diagnosed with CL were evaluated prospectively with respect to periocular involvement. RESULTS: From the 2066 patients evaluated with CL, 2622 lesions were identified. In 59 (2.9%) of these patients, a total of 66 (2.5%) lesions were located in the periocular area. Thirty-two (48.5%) of these lesions were of the papular type, 15 (22.7%) the nodulo-ulcerative type, 10 (15.2%) the plaque type, and nine (13.6%) the nodular type. Dacryocystitis was identified in four patients with periocular involvement. Over the follow-up period, no ocular or periocular deformities or complications developed in these patients. CONCLUSION: Patients suspected of CL should be evaluated and treated early in the course of their disease to prevent any permanent ocular or periocular deformities.     

An investigation of the general, reproductive and postnatal developmental toxicity of Betapol, a human milk fat equivalent.

Betapol consists of triglyceride fatty acids commonly found in vegetable and animal fats. A similarity to human milk fat indicated a potential use in infant formulae as well as for food use in general. To test the potential for substantial equivalence with a related food grade oil, palm oil, Betapol was fed to rats at 15% content in the diet using an augmented two-generation study, in order to obtain information on general (6 months), reproductive and postnatal developmental toxicity in a single study rather than separate studies. For comparison there were two control groups, namely a comparative control fed a diet containing 15% of food grade oil and a negative, or laboratory standard control fed a commercial rodent breeding diet (LAD), containing 2.3-4.7% fat. It was reasoned that if Betapol fed groups showed differences from the comparative control in the direction of the negative control these would reflect differences in the nutritional value of the high fat diets. Presence of a toxicant might be indicated by differences from the comparative control group opposite to the negative control group. The group fed 15% Betapol showed occasional, statistically significant differences from the comparative control group but the direction of difference was towards the negative control group and did not indicate the presence of an unexpected toxicant.